DNA repair - Knowledge

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by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell's survival. Thus, in a population of cells composing a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism because such mutant cells can give rise to cancer. Thus, DNA damage in frequently dividing cells, because it gives rise to mutations, is a prominent cause of cancer. In contrast, DNA damage in infrequently-dividing cells is likely a prominent cause of aging.

2535: 2976:(NHEJ) repair of a double-strand break can cause a small number of demethylations of pre-existing cytosine DNA methylations downstream of the repaired double-strand break. Further work by Allen et al. showed that NHEJ of a DNA double-strand break in a cell could give rise to some progeny cells having repressed expression of the gene harboring the initial double-strand break and some progeny having high expression of that gene due to epigenetic alterations associated with NHEJ repair. The frequency of epigenetic alterations causing repression of a gene after an NHEJ repair of a DNA double-strand break in that gene may be about 0.9%. 920:, directly joins the two ends. To guide accurate repair, NHEJ relies on short homologous sequences called microhomologies present on the single-stranded tails of the DNA ends to be joined. If these overhangs are compatible, repair is usually accurate. NHEJ can also introduce mutations during repair. Loss of damaged nucleotides at the break site can lead to deletions, and joining of nonmatching termini forms insertions or translocations. NHEJ is especially important before the cell has replicated its DNA, since there is no template available for repair by homologous recombination. There are "backup" NHEJ pathways in higher 1590:

permits differential binding of LexA to different promoters and allows for timing of the SOS response. The lesion repair genes are induced at the beginning of SOS response. The error-prone translesion polymerases, for example, UmuCD'2 (also called DNA polymerase V), are induced later on as a last resort. Once the DNA damage is repaired or bypassed using polymerases or through recombination, the amount of single-stranded DNA in cells is decreased, lowering the amounts of RecA filaments decreases cleavage activity of LexA homodimer, which then binds to the SOS boxes near promoters and restores normal gene expression.

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break. When the chromosome is replicated, this gives rise to one daughter chromosome that is heavily methylated downstream of the previous break site and one that is unmethylated in the region both upstream and downstream of the previous break site. With respect to the gene that was broken by the double-strand break, half of the progeny cells express that gene at a high level and in the other half of the progeny cells expression of that gene is repressed. When clones of these cells were maintained for three years, the new methylation patterns were maintained over that time period.

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the gut, skin, and hematopoietic system are also affected. Modern cancer treatments attempt to localize the DNA damage to cells and tissues only associated with cancer, either by physical means (concentrating the therapeutic agent in the region of the tumor) or by biochemical means (exploiting a feature unique to cancer cells in the body). In the context of therapies targeting DNA damage response genes, the latter approach has been termed 'synthetic lethality'.

10662: 3086:-Cas9) was discovered in 2012. The new technology allows anyone with molecular biology training to alter the genes of any species with precision, by inducing DNA damage at a specific point and then altering DNA repair mechanisms to insert new genes. It is cheaper, more efficient, and more precise than other technologies. With the help of CRISPR–Cas9, parts of a genome can be edited by scientists by removing, adding, or altering parts in a DNA sequence. 1638:, global transcriptional activation, genes controlling mRNA decay, and many others. A large amount of damage to a cell leaves it with an important decision: undergo apoptosis and die, or survive at the cost of living with a modified genome. An increase in tolerance to damage can lead to an increased rate of survival that will allow a greater accumulation of mutations. Yeast Rev1 and human polymerase η are members of Y family translesion DNA 10688: 3098: 9999: 3074:

regulation and by recombination and selection of alleles. On the other hand, DNA damage repair and protection does influence the rate of accumulation of irreparable, advantageous, code expanding, inheritable mutations, and slows down the evolutionary mechanism for expansion of the genome of organisms with new functionalities. The tension between evolvability and mutation repair and protection needs further investigation.

10033: 1662: 1148:. Pol ζ is unique in that it can extend terminal mismatches, whereas more processive polymerases cannot. So when a lesion is encountered, the replication fork will stall, PCNA will switch from a processive polymerase to a TLS polymerase such as Pol ι to fix the lesion, then PCNA may switch to Pol ζ to extend the mismatch, and last PCNA will switch to the processive polymerase to continue replication. 1771:, can significantly extend lifespan. The mammalian homolog of SIR-2 is known to induce downstream DNA repair factors involved in NHEJ, an activity that is especially promoted under conditions of caloric restriction. Caloric restriction has been closely linked to the rate of base excision repair in the nuclear DNA of rodents, although similar effects have not been observed in mitochondrial DNA. 896: 2436: 2423: 2414: 2400: 2391: 2384: 2375: 2359: 2348: 2332: 2325: 2318: 2296: 2289: 2267: 2260: 2247: 2229: 2218: 2200: 2189: 2169: 2158: 2142: 2131: 2122: 2100: 2093: 2073: 2066: 2059: 2039: 2032: 2025: 2816:(OGG1) is the primary enzyme responsible for the excision of the oxidized guanine during DNA repair. OGG1 finds and binds to an 8-OHdG within a few seconds. However, OGG1 does not immediately excise 8-OHdG. In HeLa cells half maximum removal of 8-OHdG occurs in 30 minutes, and in irradiated mice, the 8-OHdGs induced in the mouse liver are removed with a half-life of 11 minutes. 880:. In fact, when a double-strand break is accompanied by a cross-linkage joining the two strands at the same point, neither strand can be used as a template for the repair mechanisms, so that the cell will not be able to complete mitosis when it next divides, and will either die or, in rare cases, undergo a mutation. Three mechanisms exist to repair double-strand breaks (DSBs): 1746:. The molecular mechanisms by which such restriction results in lengthened lifespan are as yet unclear (see for some discussion); however, the behavior of many genes known to be involved in DNA repair is altered under conditions of caloric restriction. Several agents reported to have anti-aging properties have been shown to attenuate constitutive level of 147: 704:(but cells remain superficially functional when non-essential genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister 859:, the proteins involved are the Mut class proteins: MutS, MutL, and MutH. In most Eukaryotes, the analog for MutS is MSH and the analog for MutL is MLH. MutH is only present in bacteria. This is followed by removal of damaged region by an exonuclease, resynthesis by DNA polymerase, and nick sealing by DNA ligase. 652:). Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism, which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth 2680:

repair pathway for double-strand breaks. In MMEJ repair of a double-strand break, an homology of 5–25 complementary base pairs between both paired strands is sufficient to align the strands, but mismatched ends (flaps) are usually present. MMEJ removes the extra nucleotides (flaps) where strands are

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The chart in this section shows some frequent DNA damaging agents, examples of DNA lesions they cause, and the pathways that deal with these DNA damages. At least 169 enzymes are either directly employed in DNA repair or influence DNA repair processes. Of these, 83 are directly employed in repairing

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Deficiencies in DNA repair enzymes are occasionally caused by a newly arising somatic mutation in a DNA repair gene, but are much more frequently caused by epigenetic alterations that reduce or silence expression of DNA repair genes. For example, when 113 colorectal cancers were examined in sequence,

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While large numbers of epigenetic alterations are found in cancers, the epigenetic alterations in DNA repair genes, causing reduced expression of DNA repair proteins, appear to be particularly important. Such alterations are thought to occur early in progression to cancer and to be a likely cause of

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indicates that a general global stress response pathway exist at the level of transcriptional activation. In contrast, different human cell types respond to damage differently indicating an absence of a common global response. The probable explanation for this difference between yeast and human cells

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to provide a platform for the specialized polymerases to bypass the lesion and resume DNA replication. After translesion synthesis, extension is required. This extension can be carried out by a replicative polymerase if the TLS is error-free, as in the case of Pol η, yet if TLS results in a mismatch,

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either bypassing or repairing lesions at locations of stalled DNA replication. For example, Human DNA polymerase eta can bypass complex DNA lesions like guanine-thymine intra-strand crosslink, GT, although it can cause targeted and semi-targeted mutations. Paromita Raychaudhury and Ashis Basu studied

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Cells are known to eliminate three types of damage to their DNA by chemically reversing it. These mechanisms do not require a template, since the types of damage they counteract can occur in only one of the four bases. Such direct reversal mechanisms are specific to the type of damage incurred and do

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A chart of common DNA damaging agents, examples of lesions they cause in DNA, and pathways used to repair these lesions. Also shown are many of the genes in these pathways, an indication of which genes are epigenetically regulated to have reduced (or increased) expression in various cancers. It also

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Many other drugs for use against other residual DNA repair mechanisms commonly found in cancer are currently under investigation. However, synthetic lethality therapeutic approaches have been questioned due to emerging evidence of acquired resistance, achieved through rewiring of DNA damage response

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is combined with chemotherapeutics to inhibit single-strand break repair induced by DNA damage caused by the co-administered chemotherapy. Tumor cells relying on this residual DNA repair mechanism are unable to repair the damage and hence are not able to survive and proliferate, whereas normal cells

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and infections more often, and, as a consequence, have shorter lifespans than wild-type mice. In similar manner, mice deficient in a key repair and transcription protein that unwinds DNA helices have premature onset of aging-related diseases and consequent shortening of lifespan. However, not every

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variant H2AX constitutes about 10% of the H2A histones in human chromatin. γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute. The extent of

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with specific DNA polymerase knockouts. Viability was very low in a strain lacking pol II, pol IV, and pol V, the three SOS-inducible DNA polymerases, indicating that translesion synthesis is conducted primarily by these specialized DNA polymerases. A bypass platform is provided to these polymerases

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Another type of DNA double-strand breaks originates from the DNA heat-sensitive or heat-labile sites. These DNA sites are not initial DSBs. However, they convert to DSB after treating with elevated temperature. Ionizing irradiation can induces a highly complex form of DNA damage as clustered damage.

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Damage to DNA alters the spatial configuration of the helix, and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place.

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gene. Oxidative DNA damage from bromate modulated the DNA methylation pattern (caused epigenetic alterations) at CpG sites within the region of DNA studied. In untreated cells, CpGs located at −189, −134, −29, −19, +16, and +19 of the BRCA1 gene had methylated cytosines (where numbering is from the

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Replication stress, along with the selection for inactivating mutations in DNA damage response genes in the evolution of the tumor, leads to downregulation and/or loss of some DNA damage response mechanisms, and hence loss of DNA repair and/or senescence/programmed cell death. In experimental mouse

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It has become apparent over the past several years that the DNA damage response acts as a barrier to the malignant transformation of preneoplastic cells. Previous studies have shown an elevated DNA damage response in cell-culture models with oncogene activation and preneoplastic colon adenomas. DNA

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work by overwhelming the capacity of the cell to repair DNA damage, resulting in cell death. Cells that are most rapidly dividing – most typically cancer cells – are preferentially affected. The side-effect is that other non-cancerous but rapidly dividing cells such as progenitor cells in

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activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. The loss of LexA repressor induces transcription of the SOS genes and allows for further signal induction, inhibition of cell division and an increase in levels of proteins responsible for damage processing.

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Given these properties of DNA damage and mutation, it can be seen that DNA damage is a special problem in non-dividing or slowly-dividing cells, where unrepaired damage will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damage that does not kill the cell

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A certain irreducible background incidence of cancer is to be expected regardless of circumstances: mutations can never be absolutely avoided, because they are an inescapable consequence of fundamental limitations on the accuracy of DNA replication, as discussed in Chapter 5. If a human could live

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Damage to DNA is very common and is constantly being repaired. Epigenetic alterations can accompany DNA repair of oxidative damage or double-strand breaks. In human cells, oxidative DNA damage occurs about 10,000 times a day and DNA double-strand breaks occur about 10 to 50 times a cell cycle in

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residues, and polycyclic aromatic hydrocarbon adducts. DNA damage can be recognized by enzymes, and thus can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA

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downstream of the repaired double-strand break. The other DNA strand loses methylation at about six CpG sites that were previously methylated downstream of the double-strand break, as well as losing methylation at about five CpG sites that were previously methylated upstream of the double-strand

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structure and a high degree of sequence conservation. In other classes and phyla, the sequence of SOS boxes varies considerably, with different length and composition, but it is always highly conserved and one of the strongest short signals in the genome. The high information content of SOS boxes

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In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and

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in a particular species (or, in a particular gene) is a function of the rate of mutation. As a consequence, the rate and accuracy of DNA repair mechanisms have an influence over the process of evolutionary change. DNA damage protection and repair does not influence the rate of adaptation by gene

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Some of the more well studied genes central to these repair processes are shown in the chart. The gene designations shown in red, gray or cyan indicate genes frequently epigenetically altered in various types of cancers. Knowledge articles on each of the genes highlighted by red, gray or cyan

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are respectively ~3, ~30 and ~129 years. Of these, the shortest lived species, mouse, expresses DNA repair genes, including core genes in several DNA repair pathways, at a lower level than do humans and naked mole rats. Furthermore several DNA repair pathways in humans and naked mole-rats are

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Reduced expression of DNA repair genes causes deficient DNA repair. When DNA repair is deficient DNA damages remain in cells at a higher than usual level and these excess damages cause increased frequencies of mutation or epimutation. Mutation rates increase substantially in cells defective in

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The prevalence of DNA damage response mutations differs across cancer types; for example, 30% of breast invasive carcinomas have mutations in genes involved in homologous recombination. In cancer, downregulation is observed across all DNA damage response mechanisms (base excision repair (BER),

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If the rate of DNA damage exceeds the capacity of the cell to repair it, the accumulation of errors can overwhelm the cell and result in early senescence, apoptosis, or cancer. Inherited diseases associated with faulty DNA repair functioning result in premature aging, increased sensitivity to

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quickly attaches to the product of PARP1 action, a poly-ADP ribose chain, and ALC1 completes arrival at the DNA damage within 10 seconds of the occurrence of the damage. About half of the maximum chromatin relaxation, presumably due to action of ALC1, occurs by 10 seconds. This then allows

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Differential activity of DNA repair pathways across various regions of the human genome causes mutations to be very unevenly distributed within tumor genomes. In particular, the gene-rich, early-replicating regions of the human genome exhibit lower mutation frequencies than the gene-poor,

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for specialized translesion polymerases (i.e. DNA polymerase IV or V, from the Y Polymerase family), often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides. The polymerase switching is thought to be mediated by, among other factors, the

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Genes involved in DNA damage response pathways and frequently mutated in cancer (HR = homologous recombination; NHEJ = non-homologous end joining; SSA = single-strand annealing; FA = fanconi anemia pathway; BER = base excision repair; NER = nucleotide excision repair; MMR = mismatch

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nucleotide excision repair (NER), DNA mismatch repair (MMR), homologous recombination repair (HR), non-homologous end joining (NHEJ) and translesion DNA synthesis (TLS). As well as mutations to DNA damage repair genes, mutations also arise in the genes responsible for arresting the

2552:, while the majority had reduced MGMT expression due to methylation of the MGMT promoter region (an epigenetic alteration). Five different studies found that between 40% and 90% of colorectal cancers have reduced MGMT expression due to methylation of the MGMT promoter region. 1988:

to allow sufficient time for DNA repair to occur, and some genes are involved in both DNA damage repair and cell cycle checkpoint control, for example ATM and checkpoint kinase 2 (CHEK2) – a tumor suppressor that is often absent or downregulated in non-small cell lung cancer.

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MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B, White RR, Zhavoronkov A, Gladyshev VN, Seluanov A, Gorbunova V, Zhang ZD, Vijg J (2015). "DNA repair in species with extreme lifespan differences". Aging. 7 (12): 1171–84. doi:10.18632/aging.100866. PMC 4712340.

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The rate of DNA repair depends on various factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage or can no longer effectively repair its DNA may enter one of three possible states:

1085:. Translesion synthesis polymerases often have low fidelity (high propensity to insert wrong bases) on undamaged templates relative to regular polymerases. However, many are extremely efficient at inserting correct bases opposite specific types of damage. For example, 1959:

damage response mechanisms trigger cell-cycle arrest, and attempt to repair DNA lesions or promote cell death/senescence if repair is not possible. Replication stress is observed in preneoplastic cells due to increased proliferation signals from oncogenic mutations.

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Classically, cancer has been viewed as a set of diseases that are driven by progressive genetic abnormalities that include mutations in tumour-suppressor genes and oncogenes, and chromosomal aberrations. However, it has become apparent that cancer is also driven by

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The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a

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It consists of different types of DNA lesions in various locations of the DNA helix. Some of these closely located lesions can probably convert to DSB by exposure to high temperatures. But the exact nature of these lesions and their interactions is not yet known

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became the sole and universal means of encoding genetic information, requiring DNA repair mechanisms that in their basic form have been inherited by all extant life forms from their common ancestor. The emergence of Earth's oxygen-rich atmosphere (known as the

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for 30 minutes causes the mismatch repair protein heterodimer MSH2-MSH6 to recruit DNA methyltransferase 1 (DNMT1) to sites of some kinds of oxidative DNA damage. This could cause increased methylation of cytosines (epigenetic alterations) at these locations.

1048:, which is especially common in regions near an open replication fork. Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them. 7880:

Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F, Irajie C, Moradi Sarabi M, et al. (May 2013). "Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer".

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the damaged DNA backbone at the AP site. DNA polymerase then removes the damaged region using its 5' to 3' exonuclease activity and correctly synthesizes the new strand using the complementary strand as a template. The gap is then sealed by enzyme DNA

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processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day. While this constitutes at most only 0.0003125% of the human genome's approximately 3.2 billion bases, unrepaired lesions in critical genes (such as

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Higher levels of DNA damage not only cause increased mutation, but also cause increased epimutation. During repair of DNA double strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can cause epigenetic gene silencing.

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It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damage and mutation are fundamentally different. Damage results in physical abnormalities in the DNA, such as single- and double-strand breaks,

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When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of

2758:(8-OHdG) in the average mammalian cell DNA. 8-OHdG constitutes about 5% of the oxidative damages commonly present in DNA. The oxidized guanines do not occur randomly among all guanines in DNA. There is a sequence preference for the guanine at a 2939:

region). Bromate treatment-induced oxidation resulted in the loss of cytosine methylation at −189, −134, +16 and +19 while also leading to the formation of new methylation at the CpGs located at −80, −55, −21 and +8 after DNA repair was allowed.

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gene AGE-1, an upstream effector of DNA repair pathways, confers dramatically extended life span under free-feeding conditions but leads to a decrease in reproductive fitness under conditions of caloric restriction. This observation supports the

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causes breaks in DNA strands. Intermediate-level ionizing radiation may induce irreparable DNA damage (leading to replicational and transcriptional errors needed for neoplasia or may trigger viral interactions) leading to pre-mature aging and

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regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce.

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HR requires the presence of an identical or nearly identical sequence to be used as a template for repair of the break. The enzymatic machinery responsible for this repair process is nearly identical to the machinery responsible for

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it is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes. The SOS response is known to be widespread in the Bacteria domain, but it is mostly absent in some bacterial phyla, like the

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A number of individual genes have been identified as influencing variations in life span within a population of organisms. The effects of these genes is strongly dependent on the environment, in particular, on the organism's diet.

1467:(PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors. Central to all DNA damage induced checkpoints responses is a pair of large protein kinases belonging to the first group of PI3K-like protein kinases-the ATM ( 778:

and confers a level of resistance to alkylating agents upon sustained exposure by upregulation of alkylation repair enzymes. The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and adenine.

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describe the epigenetic alteration(s) and the cancer(s) in which these epimutations are found. Review articles, and broad experimental survey articles also document most of these epigenetic DNA repair deficiencies in cancers.

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Experimental animals with genetic deficiencies in DNA repair often show decreased life span and increased cancer incidence. For example, mice deficient in the dominant NHEJ pathway and in telomere maintenance mechanisms get

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Red-highlighted genes are frequently reduced or silenced by epigenetic mechanisms in various cancers. When these genes have low or absent expression, DNA damages can accumulate. Replication errors past these damages (see

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to catalyze relevant chemical reactions has played a significant role in the elaboration of repair mechanisms during evolution. For an extremely detailed review of hypotheses relating to the evolution of DNA repair, see.

4807:"Mutational specificity of gamma-radiation-induced guanine-thymine and thymine-guanine intrastrand cross-links in mammalian cells and translesion synthesis past the guanine-thymine lesion by human DNA polymerase eta" 152: 1963:

is characterized by: increased replication initiation/origin firing; increased transcription and collisions of transcription-replication complexes; nucleotide deficiency; increase in reactive oxygen species (ROS).

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Although distinctly different from each other, DNA damage and mutation are related because DNA damage often causes errors of DNA synthesis during replication or repair; these errors are a major source of mutation.

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to repair damage from UV irradiation. Another type of damage, methylation of guanine bases, is directly reversed by the enzyme methyl guanine methyl transferase (MGMT), the bacterial equivalent of which is called

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Dollé ME, Busuttil RA, Garcia AM, Wijnhoven S, van Drunen E, Niedernhofer LJ, et al. (April 2006). "Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice".

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Stenerlöw B, Karlsson KH, Cooper B, Rydberg B. "Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining".

1914:, two important genes whose mutations confer a hugely increased risk of breast cancer on carriers, are both associated with a large number of DNA repair pathways, especially NHEJ and homologous recombination. 1471:) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved in evolution. All DNA damage response requires either ATM or ATR because they have the ability to bind to the 2964:

In mice with a CRISPR-mediated homology-directed recombination insertion in their genome there were a large number of increased methylations of CpG sites within the double-strand break-associated insertion.

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of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky

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Cabelof DC, Yanamadala S, Raffoul JJ, Guo Z, Soofi A, Heydari AR (March 2003). "Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline".

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during translesion synthesis may be preferable to resorting to more drastic mechanisms of DNA repair, which may cause gross chromosomal aberrations or cell death. In short, the process involves specialized

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chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break. γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation,

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Lee KH, Lee JS, Nam JH, Choi C, Lee MC, Park CS, et al. (October 2011). "Promoter methylation status of hMLH1, hMSH2, and MGMT genes in colorectal cancer associated with adenoma-carcinoma sequence".

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caused by UV light is usually repaired by a three-step process. First the damage is recognized, then 12-24 nucleotide-long strands of DNA are removed both upstream and downstream of the damage site by

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Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, et al. (November 2006). "Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints".

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facilitates the mobilization of SIRT6 to DNA damage sites, and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs.

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of the double-strand break, the involvement of DNMT1 causes the two repaired strands of DNA to have different levels of methylated cytosines. One strand becomes frequently methylated at about 21

811:(BER): damaged single bases or nucleotides are most commonly repaired by removing the base or the nucleotide involved and then inserting the correct base or nucleotide. In base excision repair, a 5965:

Kobayashi Y, Narumi I, Satoh K, Funayama T, Kikuchi M, Kitayama S, et al. (November 2004). "Radiation response mechanisms of the extremely radioresistant bacterium Deinococcus radiodurans".

1313:. This larger complex rapidly associates with UV-induced damage within chromatin, with half-maximum association completed in 40 seconds. The PARP1 protein, attached to both DDB1 and DDB2, then 855:. These systems consist of at least two proteins. One detects the mismatch, and the other recruits an endonuclease that cleaves the newly synthesized DNA strand close to the region of damage. In 2518:

Deficient expression of DNA repair proteins due to an inherited mutation can cause increased risk of cancer. Individuals with an inherited impairment in any of 34 DNA repair genes (see article

1937:, which was approved by the Food and Drug Administration in 2015 for the treatment in women of BRCA-defective ovarian cancer. Tumor cells with partial loss of DNA damage response (specifically, 2746:). The selective advantage of DNA repair is to allow the cell to survive in the face of DNA damage. The selective advantage of epigenetic alterations that occur with DNA repair is not clear. 1605:

control, protein trafficking and degradation. Such genome wide transcriptional response is very complex and tightly regulated, thus allowing coordinated global response to damage. Exposure of

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was repressed due to promoter methylation (PMS2 protein is unstable in the absence of MLH1). In the other 10 cases, loss of PMS2 expression was likely due to epigenetic overexpression of the

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Epigenetic alterations refer to functionally relevant modifications to the genome that do not involve a change in the nucleotide sequence. Examples of such modifications are changes in

1895: 2633:, such cancers ordinarily have epigenetic deficiencies in other DNA repair genes. These repair deficiencies would likely cause increased unrepaired DNA damages. The over-expression of 8277:

Lam JS, Seligson DB, Yu H, Li A, Eeva M, Pantuck AJ, et al. (August 2006). "Flap endonuclease 1 is overexpressed in prostate cancer and is associated with a high Gleason score".

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Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. (April 2005). "Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase".

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enzyme removes the damaged base from the DNA by cleaving the bond between the base and the deoxyribose. These enzymes remove a single base to create an apurinic or apyrimidinic site (

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localizing to oxidized guanines. Polymerase beta is the main human polymerase in short-patch BER of oxidative DNA damage. Jiang et al. also found that polymerase beta recruited the

8595:"Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer" 6135:

Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, et al. (July 2004). "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase".

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for six hours, 8-OHdG increased about 3.5-fold in DNA and this caused about 80% demethylation of the 5-methylcytosines in the genome. Demethylation of CpGs in a gene promoter by

9987: 5466:

Jazayeri A, Falck J, Lukas C, Bartek J, Smith GC, Lukas J, et al. (January 2006). "ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks".

139:

The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence

42: 151: 1726: 1675:

DNA repair deficiency creates exactly the predicted effects; mice deficient in the NER pathway exhibited shortened life span without correspondingly higher rates of mutation.

9438:"Oxidative DNA Damage Modulates DNA Methylation Pattern in Human Breast Cancer 1 (BRCA1) Gene via the Crosstalk between DNA Polymerase β and a de novo DNA Methyltransferase" 548:

and tautomeric shift. Constitutive (spontaneous) DNA damage caused by endogenous oxidants can be detected as a low level of histone H2AX phosphorylation in untreated cells.

6610:

Bartkova J, Horejsí Z, Koed K, Krämer A, Tort F, Zieger K, et al. (April 2005). "DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis".

2574:

In a further example, epigenetic defects were found in various cancers (e.g. breast, ovarian, colorectal and head and neck). Two or three deficiencies in the expression of

544:

UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar

4020:

Acharya PV (1971). "The isolation and partial characterization of age-correlated oligo-deoxyribo-ribonucleotides with covalently linked aspartyl-glutamyl polypeptides".

1374:

are activated. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the

660:), which is potentially lethal to an organism. Therefore, the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer. 2681:

joined, and then ligates the strands to create an intact DNA double helix. MMEJ almost always involves at least a small deletion, so that it is a mutagenic pathway.

92:. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular 9602:"Rapid and transient recruitment of DNMT1 to DNA double-strand breaks is mediated by its interaction with multiple components of the DNA damage response machinery" 7841:"Promoter CpG island hypermethylation of the DNA repair enzyme MGMT predicts clinical response to dacarbazine in a phase II study for metastatic colorectal cancer" 1787:, which suggests that genes conferring a large survival advantage early in life will be selected for even if they carry a corresponding disadvantage late in life. 4677:

Zahradka K, Slade D, Bailone A, Sommer S, Averbeck D, Petranovic M, et al. (October 2006). "Reassembly of shattered chromosomes in Deinococcus radiodurans".

1475:

at the site of DNA damage, together with accessory proteins that are platforms on which DNA damage response components and DNA repair complexes can be assembled.

1251:

protein starts to appear at DNA damage sites in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs. PARP1 synthesizes

674:

damage, transcription of a gene can be prevented, and thus translation into a protein will also be blocked. Replication may also be blocked or the cell may die.

9988: 3057:

On some occasions, DNA damage is not repaired or is repaired by an error-prone mechanism that results in a change from the original sequence. When this occurs,

1871:") because those affected appear elderly and experience aging-related diseases at an abnormally young age, while not manifesting all the symptoms of old age. 970:

to the site for ligating the DNA ends, leading to an intact DNA. MMEJ is always accompanied by a deletion, so that MMEJ is a mutagenic pathway for DNA repair.

4520:"Microhomology-mediated End Joining and Homologous Recombination share the initial end resection step to repair DNA double-strand breaks in mammalian cells" 1894:

Because of inherent limitations in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer. There are at least 34

899:

DNA ligase, shown above repairing chromosomal damage, is an enzyme that joins broken nucleotides together by catalyzing the formation of an internucleotide

3008:); however, more complex organisms with more complex genomes have correspondingly more complex repair mechanisms. The ability of a large number of protein 2827:

to the 8-OHdG lesion (see Figure). This allows TET1 to demethylate an adjacent methylated cytosine. Demethylation of cytosine is an epigenetic alteration.

7656:"O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions" 986:

as a template. DSBs caused by the replication machinery attempting to synthesize across a single-strand break or unrepaired lesion cause collapse of the

1216:

presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action. To allow DNA repair, the chromatin must be

4856:"Genetic requirement for mutagenesis of the G[8,5-Me]T cross-link in Escherichia coli: DNA polymerases IV and V compete for error-prone bypass" 2625:

repair. They are sometimes epigenetically over-expressed and sometimes under-expressed in certain cancers. As indicated in the Knowledge articles on

2922:

protein DNMT3b to BER repair sites. They then evaluated the methylation pattern at the single nucleotide level in a small region of DNA including the

10093: 9005:"Mapping structurally defined guanine oxidation products along DNA duplexes: influence of local sequence context and endogenous cytosine methylation" 6359:

long enough, it is inevitable that at least one of his or her cells would eventually accumulate a set of mutations sufficient for cancer to develop.

2559:

expression, PMS2 was deficient in 6 due to mutations in the PMS2 gene, while in 103 cases PMS2 expression was deficient because its pairing partner

592:, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Inside mitochondria, 8322:"Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells" 804:

mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand.

4238:"Saccharomyces cerevisiae Ku70 potentiates illegitimate DNA double-strand break repair and serves as a barrier to error-prone DNA repair pathways" 1642:

present during global response to DNA damage and are responsible for enhanced mutagenesis during a global response to DNA damage in eukaryotes.

2649:

over-expression and increased homologous recombinational repair to at least partially deal with such excess DNA damages. In those cases where

1941:

repair) are dependent on another mechanism – single-strand break repair – which is a mechanism consisting, in part, of the PARP1 gene product.

1493:

is induced by both p53-dependent and p53-independent mechanisms and can arrest the cell cycle at the G1/S and G2/M checkpoints by deactivating

1164:

or chemicals are prone to acquire multiple sites of bulky DNA lesions and double-strand breaks. Moreover, DNA damaging agents can damage other

9251:

Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress induced DNA demethylation".

9057:

Zhou X, Zhuang Z, Wang W, He L, Wu H, Cao Y, et al. (September 2016). "OGG1 is essential in oxidative stress-induced DNA demethylation".

1283:

protein can be detected in association with γH2AX. RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with

10043: 4189:"Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae" 1627:

cells. In an animal different types of cells are distributed among different organs that have evolved different sensitivities to DNA damage.

876:

Double-strand breaks, in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to

4903: 10053: 7066:"Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast carcinoma" 2733:, which can be recruited by the transcription machinery, lowering somatic mutation rates in active genes and other open chromatin regions. 3954:

Reardon JT, Sancar A (2006). "Purification and characterization of Escherichia coli and human nucleotide excision repair enzyme systems".

3330: 2754:

In the steady state (with endogenous damages occurring and being repaired), there are about 2,400 oxidatively damaged guanines that form

2522:) have an increased risk of cancer, with some defects causing up to a 100% lifetime chance of cancer (e.g. p53 mutations). However, such 695: 420:, in which the wrong DNA base is stitched into place in a newly forming DNA strand, or a DNA base is skipped over or mistakenly inserted. 8189:"Epigenetic screen of human DNA repair genes identifies aberrant promoter methylation of NEIL1 in head and neck squamous cell carcinoma" 5992:

Spindler SR (September 2005). "Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction".

5135:"JNK Phosphorylates SIRT6 to Stimulate DNA Double-Strand Break Repair in Response to Oxidative Stress by Recruiting PARP1 to DNA Breaks" 9651:"DNA damage and Repair Modify DNA methylation and Chromatin Domain of the Targeted Locus: Mechanism of allele methylation polymorphism" 8956:"A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA" 1430:

has also been identified. These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins.

5730:

Schlacher K, Pham P, Cox MM, Goodman MF (February 2006). "Roles of DNA polymerase V and RecA protein in SOS damage-induced mutation".

5509:

Bakkenist CJ, Kastan MB (January 2003). "DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation".

4287:"Efficient processing of DNA ends during yeast nonhomologous end joining. Evidence for a DNA polymerase beta (Pol4)-dependent pathway" 1601:

cells exposed to DNA damaging agents also activate important defensive pathways by inducing multiple proteins involved in DNA repair,

708:

as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as

514:

residues per genome per generation) is too high in these species to be repaired by normal repair machinery, hence a possibility of an

3663: 2693:

hypomethylated, and this contributes to progression to endometrial cancer and BRCA-mutated serous ovarian cancer. Other genes in the

1899: 1235:

Chromatin relaxation occurs rapidly at the site of a DNA damage. In one of the earliest steps, the stress-activated protein kinase,

76:

per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to

10085: 4968:

Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T. (2006). DNA Repair and Mutagenesis, part 3. ASM Press. 2nd ed.

1355:

are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation of the cell cycle checkpoint protein

7462:"Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island" 3358: 10595: 2549: 10107: 7194: 1561:. The most common cellular signals activating the SOS response are regions of single-stranded DNA (ssDNA), arising from stalled 10569: 2682: 1976:), leading to increased tumor size and invasiveness. Humans born with inherited defects in DNA repair mechanisms (for example, 1403: 1352: 959: 536:

found in smoke, soot and tar create a huge diversity of DNA adducts- ethanoates, oxidized bases, alkylated phosphodiesters and

8363:"Flap endonuclease 1 is a promising candidate biomarker in gastric cancer and is involved in cell proliferation and apoptosis" 5375:"Dynamic in vivo interaction of DDB2 E3 ubiquitin ligase with UV-damaged DNA is independent of damage-recognition protein XPC" 8104: 6351: 5598: 5569: 4004: 3971: 3931: 3906: 3432: 3284:

Browner WS, Kahn AJ, Ziv E, Reiner AP, Oshima J, Cawthon RM, et al. (December 2004). "The genetics of human longevity".

3260: 3225: 1406:. ATM responds to DNA double-strand breaks and disruptions in chromatin structure, whereas ATR primarily responds to stalled 998:

system, MMEJ occurred in mammalian cells at the levels of 10–20% of HR when both HR and NHEJ mechanisms were also available.

10048: 2657:

are under-expressed, this would itself lead to increased unrepaired DNA damages. Replication errors past these damages (see

1829:

Mental retardation often accompanies the latter two disorders, suggesting increased vulnerability of developmental neurons.

1713:, the most radiation-resistant known organism, exhibit remarkable resistance to the double-strand break-inducing effects of 958:(PARP1) is required and may be an early step in MMEJ. There is pairing of microhomology regions followed by recruitment of 10230: 10102: 7318:"Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6" 6522:

Goldstein M, Kastan MB (2015). "The DNA damage response: implications for tumor responses to radiation and chemotherapy".

2769:

and where the cytosine is methylated (5-mCpG)). A 5-mCpG site has the lowest ionization potential for guanine oxidation.

924:. Besides its role as a genome caretaker, NHEJ is required for joining hairpin-capped double-strand breaks induced during 10285: 1019: 17: 10538: 10469: 9884:"Sudden origins: a general mechanism of evolution based on stress protein concentration and rapid environmental change" 6084:

Tissenbaum HA, Guarente L (March 2001). "Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans".

2766: 2698: 2694: 2673: 2539:

shows genes in the error-prone microhomology-mediated end joining pathway with increased expression in various cancers.

1464: 1452:

is damaged. It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide.

1321:. Action of ALC1 relaxes the chromatin at the site of UV damage to DNA. This relaxation allows other proteins in the 1129: 885: 8544:"Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer" 6972:, Ohm JE (February 2006). "Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?". 3045:, necessitated the evolution of DNA repair mechanisms that act specifically to counter the types of damage induced by 1487: 6766:

Halazonetis TD, Gorgoulis VG, Bartek J (March 2008). "An oncogene-induced DNA damage model for cancer development".

10553: 3127: 2805: 2743: 1614:

to DNA damaging agents results in overlapping but distinct transcriptional profiles. Similarities to environmental

188: 3491:"Constitutive histone H2AX phosphorylation and ATM activation, the reporters of DNA damage by endogenous oxidants" 1035: 9938: 1244: 533: 4737: 2804:

targets 8-OHdG and binds to the lesion without immediate excision. OGG1, present at a 5mCp-8-OHdG site recruits

4448: 4440: 3147: 2519: 1796: 3614:

Campisi J, d'Adda di Fagagna F (September 2007). "Cellular senescence: when bad things happen to good cells".

608:, create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the 8706:"Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes" 8403: 3729:

Sancar A (June 2003). "Structure and function of DNA photolyase and cryptochrome blue-light photoreceptors".

1468: 1456: 1399: 1348: 1274:

is also involved in the early steps leading to chromatin decondensation after DNA double-strand breaks. The

1145: 1014:

and other sources. At least two copies of the genome, with random DNA breaks, can form DNA fragments through

700:

Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the

9759:"Non-homologous end joining induced alterations in DNA methylation: A source of permanent epigenetic change" 9337:"Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins" 5083:"The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage" 10528: 10435: 6422:

Gavande NS, VanderVere-Carozza PS, Hinshaw HD, Jalal SI, Sears CR, Pawelczak KS, et al. (April 2016).

3157: 1255: 729:

upon irradiation with UV light results in an abnormal covalent bond between adjacent pyrimidine bases. The

502:

bases from the DNA backbone) and single-strand breaks. For example, hydrolytic depurination is seen in the

330: 10090: 9143:"Lost in the Crowd: How Does Human 8-Oxoguanine DNA Glycosylase 1 (OGG1) Find 8-Oxoguanine in the Genome?" 8904:"Endogenous versus exogenous DNA adducts: their role in carcinogenesis, epidemiology, and risk assessment" 2491:, last for multiple cell generations, and can be considered to be epimutations (equivalent to mutations). 2483:. Each of these epigenetic alterations serves to regulate gene expression without altering the underlying 766:. This is an expensive process because each MGMT molecule can be used only once; that is, the reaction is 10718: 10713: 10037: 8187:

Chaisaingmongkol J, Popanda O, Warta R, Dyckhoff G, Herpel E, Geiselhart L, et al. (December 2012).

6271:

Walker DW, McColl G, Jenkins NL, Harris J, Lithgow GJ (May 2000). "Evolution of lifespan in C. elegans".

5615: 4043:

Bjorksten J, Acharya PV, Ashman S, Wetlaufer DB (July 1971). "Gerogenic fractions in the tritiated rat".

3198: 1973: 1695:

up-regulated compared to mouse. These observations suggest that elevated DNA repair facilitates greater

1437: 1314: 7367:"Disruption of Brca2 increases the spontaneous mutation rate in vivo: synergism with ionizing radiation" 7259:"Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2" 2598:) can lead to increased mutations and, ultimately, cancer. Epigenetic repression of DNA repair genes in 2555:

Similarly, out of 119 cases of mismatch repair-deficient colorectal cancers that lacked DNA repair gene

10678: 10457: 10281: 10274: 9847:

O'Brien PJ (February 2006). "Catalytic promiscuity and the divergent evolution of DNA repair enzymes".

9708:"Detection of CRISPR-mediated genome modifications through altered methylation patterns of CpG islands" 3132: 2973: 2793: 2755: 2730: 1929:

Perhaps the most well-known of these 'synthetic lethality' drugs is the poly(ADP-ribose) polymerase 1 (

1651: 1322: 1026:

that can continue extension until complementary partner strands are found. In the final step, there is

881: 830: 758: 192: 7839:

Amatu A, Sartore-Bianchi A, Moutinho C, Belotti A, Bencardino K, Chirico G, et al. (April 2013).

10023: 7064:

Baldassarre G, Battista S, Belletti B, Thakur S, Pentimalli F, Trapasso F, et al. (April 2003).

5321:

Luijsterburg MS, Acs K, Ackermann L, Wiegant WW, Bekker-Jensen S, Larsen DH, et al. (May 2012).

3112: 3042: 2534: 1868: 1229: 954:

nuclease on either side of a double-strand break to reveal microhomology regions. In further steps,

877: 605: 9962: 8804:"Clustered Mutation Signatures Reveal that Error-Prone DNA Repair Targets Mutations to Active Genes" 8454:"Exploration of global gene expression patterns in pancreatic adenocarcinoma using cDNA microarrays" 8074: 7744:

Psofaki V, Kalogera C, Tzambouras N, Stephanou D, Tsianos E, Seferiadis K, et al. (July 2010).

6920:"CHK2 kinase expression is down-regulated due to promoter methylation in non-small cell lung cancer" 6224:"Mitochondrial and nuclear DNA base excision repair are affected differently by caloric restriction" 5373:

Luijsterburg MS, Goedhart J, Moser J, Kool H, Geverts B, Houtsmuller AB, et al. (August 2007).

5272:

Mailand N, Bekker-Jensen S, Faustrup H, Melander F, Bartek J, Lukas C, et al. (November 2007).

3450:"UV Sensitivity and Mutagenesis of the Extremely Thermophilic Eubacterium Thermus thermophilus HB27" 3298: 1418:

cascade, eventually leading to cell cycle arrest. A class of checkpoint mediator proteins including

10452: 10374: 10223: 9335:

Maeder ML, Angstman JF, Richardson ME, Linder SJ, Cascio VM, Tsai SQ, et al. (December 2013).

3683: 2953: 2622: 2508: 1938: 1813:: hypersensitivity to sunlight/UV, resulting in increased skin cancer incidence and premature aging 1610: 1540: 1236: 889: 738: 206:) can impede a cell's ability to carry out its function and appreciably increase the likelihood of 164: 96:

does not occur, irreparable DNA damage may occur. This can eventually lead to malignant tumors, or

9922: 8755:"The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSα" 8452:

Iacobuzio-Donahue CA, Maitra A, Olsen M, Lowe AW, van Heek NT, Rosty C, et al. (April 2003).

5323:"A new non-catalytic role for ubiquitin ligase RNF8 in unfolding higher-order chromatin structure" 5274:"RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins" 2792:-pG, or 5mCpG. Reactive oxygen species (ROS) may attack guanine at the dinucleotide site, forming 2526:(which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers. 795:

excising a hydrolytically-produced uracil residue from DNA. The uracil residue is shown in yellow.

10060: 9706:

Farris MH, Texter PA, Mora AA, Wiles MV, Mac Garrigle EF, Klaus SA, et al. (December 2020).

8853:

Polak P, Lawrence MS, Haugen E, Stoletzki N, Stojanov P, Thurman RE, et al. (January 2014).

5417:

Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, et al. (October 2012).

5187:"PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites" 4907: 3331:"Nobel Prize in Chemistry Awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar for DNA Studies" 2985: 2863:

was reduced (an epigenetic alteration) and this allowed about 6.5 fold increase of expression of

1709: 1498: 1098: 1006: 670: 593: 262: 77: 9952: 8503:"Increased expression and no mutation of the Flap endonuclease (FEN1) gene in human lung cancer" 6561: 6037:"Potential anti-aging agents suppress the level of constitutive mTOR- and DNA damage- signaling" 2772: 10564: 10474: 10269: 9808:"Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans" 7611:

Fearon ER (November 1997). "Human cancer syndromes: clues to the origin and nature of cancer".

5133:

Van Meter M, Simon M, Tombline G, May A, Morello TD, Hubbard BP, et al. (September 2016).

3678: 3293: 2813: 2801: 2784:. In adult somatic cells DNA methylation typically occurs in the context of CpG dinucleotides ( 1767: 1631: 1630:

In general global response to DNA damage involves expression of multiple genes responsible for

1221: 1132:(PCNA). Under normal circumstances, PCNA bound to polymerases replicates the DNA. At a site of 852: 792: 601: 7703:

Shen L, Kondo Y, Rosner GL, Xiao L, Hernandez NS, Vilaythong J, et al. (September 2005).

5849:

de Boer J, Andressoo JO, de Wit J, Huijmans J, Beems RB, van Steeg H, et al. (May 2002).

5419:"PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1" 5185:

Haince JF, McDonald D, Rodrigue A, Déry U, Masson JY, Hendzel MJ, et al. (January 2008).

2511:

repair (HRR). Chromosomal rearrangements and aneuploidy also increase in HRR defective cells.

2471:, changes in chromosomal architecture (caused by inappropriate expression of proteins such as 1898:. Many of these mutations cause DNA repair to be less effective than normal. In particular, 640:

that cap chromosomes and undergo partial degradation each time a cell undergoes division (see

10330: 8501:

Sato M, Girard L, Sekine I, Sunaga N, Ramirez RD, Kamibayashi C, et al. (October 2003).

8402:

Krause A, Combaret V, Iacono I, Lacroix B, Compagnon C, Bergeron C, et al. (July 2005).

7416:"Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients" 4417: 2949: 2919: 2582:

or PMS2 occur simultaneously in the majority of 49 colon cancers evaluated by Facista et al.

1856: 1810: 1635: 1602: 1371: 1340: 1044:

introduce both single- and double-strand breaks in the course of changing the DNA's state of

1027: 983: 975: 503: 266: 203: 123: 8855:"Reduced local mutation density in regulatory DNA of cancer genomes is linked to DNA repair" 8646:"Differential DNA mismatch repair underlies mutation rate variation across the human genome" 8230:"Overexpression and hypomethylation of flap endonuclease 1 gene in breast and other cancers" 8138:

Krishnan K, Steptoe AL, Martin HC, Wani S, Nones K, Waddell N, et al. (February 2013).

6373:"The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers" 5081:

Sellou H, Lebeaupin T, Chapuis C, Smith R, Hegele A, Singh HR, et al. (December 2016).

3020:

indicates that single-cell life began to proliferate on the planet at some point during the

845:. In eukaryotes, many more proteins are involved, although the general strategy is the same. 584:. In either state the DNA is highly compacted and wound up around bead-like proteins called 265:

produced from normal metabolic byproducts (spontaneous mutation), especially the process of

10255: 10169: 10019: 9662: 9549:

Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).

9500: 9386:"Mismatch repair proteins recruit DNA methyltransferase 1 to sites of oxidative DNA damage" 9205: 8657: 7978: 7965:

Valeri N, Gasparini P, Fabbri M, Braconi C, Veronese A, Lovat F, et al. (April 2010).

7620: 7511:

Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, et al. (July 2007).

7270: 6874: 6775: 6673: 6619: 6480: 6144: 6093: 5916: 5862: 5778: 5518: 4758:"Eukaryotic translesion polymerases and their roles and regulation in DNA damage tolerance" 4686: 4531: 4143: 3850: 3461: 2911: 2797: 2715: 2468: 1977: 1902:(HNPCC) is strongly associated with specific mutations in the DNA mismatch repair pathway. 1836: 1569:

to separate the two DNA strands. In the initiation step, RecA protein binds to ssDNA in an

1333: 1225: 1217: 1184:. The accumulation of damage, to be specific, double-strand breaks or adducts stalling the 808: 613: 211: 33: 9649:

Russo G, Landi R, Pezone A, Morano A, Zuchegna C, Romano A, et al. (September 2016).

8026:"Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer" 7926:"Immunohistochemical analysis reveals high frequency of PMS2 defects in colorectal cancer" 7924:

Truninger K, Menigatti M, Luz J, Russell A, Haider R, Gebbers JO, et al. (May 2005).

6315: 3766:"Evolution of mutation rates: phylogenomic analysis of the photolyase/cryptochrome family" 3704: 3082:

A technology named clustered regularly interspaced short palindromic repeat (shortened to

3069:, the mutation has the potential to be passed on to the organism's offspring. The rate of 2968: 8: 10728: 10708: 10665: 10352: 10216: 10004: 9192:

Lan L, Nakajima S, Oohata Y, Takao M, Okano S, Masutani M, et al. (September 2004).

8954:

Hamilton ML, Guo Z, Fuller CD, Van Remmen H, Ward WF, Austad SN, et al. (May 2001).

6818: 5802:"Shorter telomeres, accelerated ageing and increased lymphoma in DNA-PKcs-deficient mice" 3162: 2936: 2923: 2842:

activity increases transcription of the gene into messenger RNA. In cells treated with H

2722: 2504: 1822: 1784: 1735: 1415: 1343:

are activated to allow DNA repair to occur before the cell cycle progresses. First, two

1106: 1015: 925: 851:

systems are present in essentially all cells to correct errors that are not corrected by

842: 597: 537: 470: 345: 113: 88:

in the cell's genome, which affect the survival of its daughter cells after it undergoes

10173: 9666: 9504: 9209: 8704:

Zheng CL, Wang NJ, Chung J, Moslehi H, Sanborn JZ, Hur JS, et al. (November 2014).

8661: 8024:

Facista A, Nguyen H, Lewis C, Prasad AR, Ramsey L, Zaitlin B, et al. (April 2012).

7982: 7624: 7274: 6878: 6779: 6677: 6623: 6484: 6148: 6097: 5920: 5866: 5522: 5029:"Cytometric detection of chromatin relaxation, an early reporter of DNA damage response" 4690: 4579:"Homology and enzymatic requirements of microhomology-dependent alternative end joining" 4535: 4147: 3854: 3465: 3359:"The Nobel Prize in Chemistry 2015 – DNA repair – providing chemical stability for life" 1968:

models, loss of DNA damage response-mediated cell senescence was observed after using a

1097:

introduces mutations at these sites. Pol η is known to add the first adenine across the

10192: 10157: 10139: 10114: 9783: 9758: 9734: 9707: 9683: 9650: 9626: 9601: 9577: 9550: 9523: 9488: 9464: 9437: 9410: 9385: 9361: 9336: 9312: 9287: 9169: 9142: 9118: 9093: 9029: 9004: 8928: 8903: 8879: 8854: 8779: 8754: 8730: 8705: 8678: 8645: 8621: 8594: 8570: 8543: 8478: 8453: 8434: 8302: 8254: 8229: 8164: 8139: 8115: 8052: 8025: 8001: 7966: 7906: 7821: 7772: 7745: 7680: 7655: 7588: 7563: 7539: 7512: 7488: 7461: 7432: 7415: 7391: 7366: 7342: 7317: 7234: 7207: 7180: 7155: 7041: 7016: 6997: 6895: 6862: 6799: 6748: 6697: 6643: 6592: 6504: 6448: 6423: 6399: 6372: 6320: 6296: 6253: 6168: 6117: 6061: 6036: 6017: 5888: 5826: 5801: 5587: 5542: 5491: 5443: 5418: 5347: 5322: 5303: 5159: 5134: 5107: 5082: 5053: 5028: 5004: 4979: 4880: 4855: 4831: 4806: 4782: 4757: 4756:

Waters LS, Minesinger BK, Wiltrout ME, D'Souza S, Woodruff RV, Walker GC (March 2009).

4710: 4654: 4627: 4603: 4578: 4554: 4519: 4497: 4253: 4169: 4068: 4056: 3874: 3790: 3765: 3639: 3515: 3490: 3335: 3030: 2907: 2690: 2496: 1960: 1806:

Defects in the NER mechanism are responsible for several genetic disorders, including:

1751: 1547: 1157: 1086: 1011: 978:

during meiosis. This pathway allows a damaged chromosome to be repaired using a sister

653: 477: 246:(in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. 235: 101: 9824: 9807: 9436:

Jiang Z, Lai Y, Beaver JM, Tsegay PS, Zhao ML, Horton JK, et al. (January 2020).

9228: 9193: 8902:

Swenberg JA, Lu K, Moeller BC, Gao L, Upton PB, Nakamura J, et al. (March 2011).

8469: 8404:"Genome-wide analysis of gene expression in neuroblastomas detected by mass screening" 7090: 7065: 6946: 6919: 6535: 6200: 4942: 4484: 4467: 4401: 4376: 4352: 4327: 4262: 4237: 4213: 4188: 3963: 3061:

may propagate into the genomes of the cell's progeny. Should such an event occur in a

2808:

and TET1 oxidizes the 5mC adjacent to the 8-OHdG. This initiates demethylation of 5mC.

1573:

driven reaction creating RecA–ssDNA filaments. RecA–ssDNA filaments activate LexA auto

10723: 10548: 10197: 10156:

Morales ME, Derbes RS, Ade CM, Ortego JC, Stark J, Deininger PL, et al. (2016).

10144: 9905: 9864: 9829: 9788: 9739: 9688: 9631: 9582: 9528: 9469: 9415: 9366: 9317: 9268: 9233: 9174: 9123: 9074: 9034: 8985: 8980: 8955: 8933: 8884: 8835: 8784: 8735: 8683: 8626: 8575: 8524: 8483: 8426: 8384: 8343: 8294: 8290: 8259: 8210: 8169: 8120: 8100: 8087:

Jin B, Robertson KD (2013). "DNA Methyltransferases, DNA Damage Repair, and Cancer".

8057: 8006: 7947: 7898: 7862: 7813: 7777: 7726: 7685: 7636: 7593: 7544: 7493: 7437: 7396: 7347: 7298: 7293: 7258: 7239: 7185: 7136: 7095: 7046: 7032: 6989: 6969: 6951: 6900: 6843: 6791: 6740: 6689: 6635: 6584: 6539: 6496: 6453: 6439: 6404: 6347: 6288: 6245: 6204: 6160: 6109: 6066: 6009: 5974: 5932: 5880: 5831: 5782: 5765:

Fry RC, Begley TJ, Samson LD (2004). "Genome-wide responses to DNA-damaging agents".

5747: 5712: 5707: 5690: 5668: 5627: 5594: 5565: 5534: 5483: 5448: 5396: 5352: 5295: 5254: 5208: 5164: 5112: 5058: 5009: 4946: 4885: 4836: 4787: 4739: 4702: 4659: 4608: 4559: 4489: 4429: 4406: 4357: 4308: 4267: 4218: 4161: 4112: 4060: 4025: 4000: 3977: 3967: 3927: 3902: 3866: 3823: 3795: 3746: 3696: 3631: 3596: 3561: 3520: 3428: 3405: 3311: 3266: 3256: 3142: 2903: 2777: 2545: 2523: 1969: 1816: 1679: 1288: 1161: 947: 775: 730: 529: 515: 454: 386: 382: 218: 10077: 8438: 8306: 7910: 7081: 6803: 6752: 6596: 6257: 6172: 5892: 5307: 4577:

Sharma S, Javadekar SM, Pandey M, Srivastava M, Kumari R, Raghavan SC (March 2015).

4501: 4072: 3878: 3643: 3251:

Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, et al. (2004).

2935:

transcription start site, and negative numbers indicate nucleotides in the upstream

2886:

incubation appear to promote other epigenetic alterations. Treatment of cells with H

10187: 10177: 10134: 10126: 10072: 9895: 9856: 9819: 9778: 9770: 9729: 9719: 9678: 9670: 9621: 9613: 9572: 9562: 9518: 9508: 9459: 9449: 9405: 9397: 9356: 9348: 9307: 9299: 9260: 9223: 9213: 9164: 9154: 9113: 9105: 9066: 9024: 9016: 9003:

Ming X, Matter B, Song M, Veliath E, Shanley R, Jones R, et al. (March 2014).

8975: 8967: 8923: 8915: 8874: 8866: 8825: 8815: 8774: 8766: 8725: 8717: 8673: 8665: 8616: 8606: 8565: 8555: 8514: 8473: 8465: 8418: 8374: 8333: 8286: 8249: 8241: 8200: 8159: 8151: 8110: 8092: 8047: 8037: 7996: 7986: 7937: 7890: 7852: 7825: 7805: 7767: 7757: 7746:"Promoter methylation status of hMLH1, MGMT, and CDKN2A/p16 in colorectal adenomas" 7716: 7675: 7667: 7628: 7583: 7575: 7534: 7524: 7483: 7473: 7427: 7386: 7378: 7337: 7329: 7316:

Hegan DC, Narayanan L, Jirik FR, Edelmann W, Liskay RM, Glazer PM (December 2006).

7288: 7278: 7229: 7219: 7175: 7167: 7126: 7085: 7077: 7036: 7028: 7001: 6981: 6941: 6931: 6890: 6882: 6833: 6783: 6732: 6724: 6715:

Gaillard H, García-Muse T, Aguilera A (May 2015). "Replication stress and cancer".

6701: 6681: 6647: 6627: 6576: 6531: 6508: 6488: 6443: 6435: 6394: 6384: 6300: 6280: 6235: 6196: 6152: 6121: 6101: 6056: 6048: 6021: 6001: 5924: 5870: 5821: 5813: 5800:

Espejel S, Martín M, Klatt P, Martín-Caballero J, Flores JM, Blasco MA (May 2004).

5774: 5739: 5702: 5658: 5546: 5526: 5495: 5475: 5438: 5430: 5386: 5342: 5334: 5285: 5244: 5198: 5154: 5146: 5102: 5094: 5048: 5040: 4999: 4991: 4938: 4929:

Wang Z (July 2001). "Translesion synthesis by the UmuC family of DNA polymerases".

4875: 4867: 4826: 4818: 4777: 4769: 4733: 4714: 4694: 4649: 4639: 4598: 4590: 4549: 4539: 4479: 4421: 4396: 4388: 4347: 4339: 4298: 4257: 4249: 4208: 4200: 4173: 4151: 4102: 4052: 3959: 3858: 3785: 3777: 3738: 3688: 3623: 3588: 3551: 3510: 3502: 3469: 3401: 3397: 3303: 3046: 3009: 2851: 2789: 1739: 1562: 1552: 1519: 1407: 1326: 1317:(creates a poly-ADP ribose chain) on DDB2 that attracts the DNA remodeling protein 1302: 1185: 987: 834: 726: 648:

is a reversible state of cellular dormancy that is unrelated to genome damage (see

449: 238:

and therefore damage or disturbance does not occur at that level. DNA is, however,

73: 9264: 9194:"In situ analysis of repair processes for oxidative DNA damage in mammalian cells" 9070: 8245: 7857: 7840: 7632: 7382: 3556: 3539: 2676:(MMEJ) pathway and are up-regulated in cancer. MMEJ is an additional error-prone 1972:(shRNA) to inhibit the double-strand break response kinase ataxia telangiectasia ( 369:

of bases and generation of DNA strand interruptions from reactive oxygen species,

10264: 10182: 10097: 9567: 8721: 8422: 7942: 7925: 7529: 7478: 5928: 5150: 3841:

Volkert MR (1988). "Adaptive response of Escherichia coli to alkylation damage".

3307: 3137: 3024:

period, although exactly when recognizably modern life first emerged is unclear.

2759: 2711: 2464: 1514: 1411: 1061: 933: 929: 848: 820: 812: 801: 417: 349: 140: 8096: 6035:

Halicka HD, Zhao H, Li J, Lee YS, Hsieh TC, Wu JM, et al. (December 2012).

3220: 2704: 1738:

reproducibly results in extended lifespan in a variety of organisms, likely via

10692: 9957: 9724: 9600:

Ha K, Lee GE, Palii SS, Brown KD, Takeda Y, Liu K, et al. (January 2011).

9109: 8820: 8803: 8770: 8338: 8321: 8091:. Advances in Experimental Medicine and Biology. Vol. 754. pp. 3–29. 7971:

Proceedings of the National Academy of Sciences of the United States of America

7263:

Proceedings of the National Academy of Sciences of the United States of America

6339: 5290: 5273: 4995: 4524:

Proceedings of the National Academy of Sciences of the United States of America

3167: 3103: 3034: 2915: 2860: 2603: 1946:

can repair the damage with the functioning homologous recombination mechanism.

1875: 1842: 1743: 1687: 1615: 1570: 1460: 1110: 1073: 767: 641: 525: 360:

There are several types of damage to DNA due to endogenous cellular processes:

53: 9774: 8320:

Kim JM, Sohn HY, Yoon SY, Oh JH, Yang JO, Kim JH, et al. (January 2005).

7894: 7809: 6838: 6005: 5691:"Aeons of distress: an evolutionary perspective on the bacterial SOS response" 5233:"DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139" 2943: 2749: 1060:

Translesion synthesis (TLS) is a DNA damage tolerance process that allows the

868: 10702: 10576: 10397: 9487:

Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, Leonhardt H (June 2005).

8971: 7762: 7579: 5817: 4644: 4343: 4303: 4286: 3827: 3489:

Tanaka T, Halicka HD, Huang X, Traganos F, Darzynkiewicz Z (September 2006).

3017: 2997: 2932: 2899: 2488: 1879: 1714: 1620: 1201: 1065: 1041: 940: 637: 581: 365: 168: 9513: 9218: 8919: 8611: 7991: 7671: 7333: 7131: 7114: 6787: 6389: 6156: 5875: 5850: 5249: 5232: 5098: 4544: 3781: 3448:

Ohta T, Tokishita SI, Mochizuki K, Kawase J, Sakahira M, Yamagata H (2006).

3270: 1243:

on serine 10 in response to double-strand breaks or other DNA damage. This

1232:

are two predominant factors employed to accomplish this remodeling process.

632:, is a protective response to the shortening of the chromosome ends, called 10543: 10512: 10462: 10445: 10392: 10345: 10201: 10148: 9909: 9868: 9833: 9792: 9743: 9692: 9635: 9586: 9532: 9473: 9419: 9384:

Ding N, Bonham EM, Hannon BE, Amick TR, Baylin SB, O'Hagan HM (June 2016).

9370: 9321: 9272: 9237: 9178: 9127: 9078: 9038: 8989: 8937: 8888: 8839: 8788: 8739: 8687: 8630: 8579: 8528: 8519: 8502: 8487: 8430: 8388: 8379: 8362: 8347: 8298: 8263: 8228:

Singh P, Yang M, Dai H, Yu D, Huang Q, Tan W, et al. (November 2008).

8214: 8173: 8155: 8124: 8061: 8010: 7951: 7902: 7866: 7817: 7781: 7730: 7689: 7597: 7548: 7497: 7400: 7351: 7283: 7243: 7189: 7140: 7099: 7050: 6993: 6955: 6936: 6904: 6847: 6795: 6744: 6693: 6639: 6588: 6543: 6500: 6457: 6408: 6292: 6249: 6208: 6164: 6113: 6070: 6013: 5978: 5936: 5884: 5835: 5786: 5751: 5716: 5672: 5663: 5646: 5631: 5538: 5487: 5452: 5400: 5356: 5338: 5299: 5212: 5203: 5186: 5168: 5116: 5062: 5027:

Halicka HD, Zhao H, Podhorecka M, Traganos F, Darzynkiewicz Z (July 2009).

5013: 4950: 4889: 4840: 4791: 4743: 4706: 4663: 4612: 4563: 4493: 4433: 4410: 4361: 4312: 4116: 4107: 4090: 3981: 3799: 3750: 3700: 3635: 3600: 3592: 3565: 3524: 3409: 3315: 3152: 3038: 3025: 2484: 1922: 1918: 1883: 1566: 1510: 1258:(poly (ADP-ribose) or PAR) chains on itself. Next the chromatin remodeler 1173: 1078: 1002: 838: 774:. A generalized response to methylating agents in bacteria is known as the 565: 561: 560:

cells in general, DNA is found in two cellular locations – inside the

495: 466: 401: 172: 10130: 9401: 8560: 8042: 7721: 7705:"MGMT promoter methylation and field defect in sporadic colorectal cancer" 7704: 7640: 7441: 7302: 7224: 7171: 6240: 6052: 5434: 5258: 4773: 4594: 4425: 4375:

Wang H, Perrault AR, Takeda Y, Qin W, Wang H, Iliakis G (September 2003).

4271: 4222: 4204: 4165: 4064: 4029: 3870: 3862: 3692: 3579:

Lynch MD (February 2006). "How does cellular senescence prevent cancer?".

2661:) could cause increased mutations and cancer, so that under-expression of 1707:). On the other hand, organisms with enhanced DNA repair systems, such as 1394:

checkpoint also exists. Checkpoint activation is controlled by two master

787: 430:

Damage caused by exogenous agents comes in many forms. Some examples are:

10158:"Heavy Metal Exposure Influences Double Strand Break DNA Repair Outcomes" 9617: 9454: 9303: 9159: 9094:"The genomics of oxidative DNA damage, repair, and resulting mutagenesis" 8205: 8188: 7879: 5044: 4518:

Truong LN, Li Y, Shi LZ, Hwang PY, He J, Wang H, et al. (May 2013).

4392: 3506: 3474: 3449: 3366: 3177: 3021: 2989: 2839: 2824: 2457: 1762: 1586: 1558: 1524: 1165: 1115: 1090: 577: 545: 507: 483: 397: 378: 282: 176: 10007:

was created from a revision of this article dated 17 June 2005

8669: 7365:

Tutt AN, van Oostrom CT, Ross GM, van Steeg H, Ashworth A (March 2002).

6736: 6685: 6631: 6492: 6222:

Stuart JA, Karahalil B, Hogue BA, Souza-Pinto NC, Bohr VA (March 2004).

5530: 4698: 4089:

Liang L, Deng L, Chen Y, Li GC, Shao C, Tischfield JA (September 2005).

962:(FEN1) to remove overhanging flaps. This is followed by recruitment of 84:

that the affected DNA encodes. Other lesions induce potentially harmful

10479: 10300: 9900: 9883: 8830: 7257:

Narayanan L, Fritzell JA, Baker SM, Liskay RM, Glazer PM (April 1997).

6580: 5391: 5374: 4437:. If this is an intentional citation to a such a paper, please replace 3182: 3122: 2993: 2969:

Non-homologous end joining can cause some epigenetic marker alterations

2641:

seen in these cancers may reflect selective pressures for compensatory

1985: 1780: 1755: 1717:, likely due to enhanced efficiency of DNA repair and especially NHEJ. 1639: 1598: 1472: 1441: 1368: 1337: 1197: 937: 913: 823: 742: 734: 649: 589: 573: 557: 407: 392: 373: 306: 258: 198: 65: 9860: 9757:

Allen B, Pezone A, Porcellini A, Muller MT, Masternak MM (June 2017).

9674: 9020: 8753:

Li F, Mao G, Tong D, Huang J, Gu L, Yang W, et al. (April 2013).

6886: 6424:"DNA repair targeted therapy: The past or future of cancer treatment?" 5743: 4871: 4822: 4328:"Processing of DNA for nonhomologous end-joining by cell-free extract" 3742: 3540:"Oncogene-induced senescence: putting the brakes on tumor development" 3388:

Roulston A, Marcellus RC, Branton PE (1999). "Viruses and apoptosis".

2830:

As an example, when human mammary epithelial cells were treated with H

1765:

of the gene SIR-2, which regulates DNA packaging in the nematode worm

725:

not involve breakage of the phosphodiester backbone. The formation of

656:. Unregulated cell division can lead to the formation of a tumor (see 9352: 8870: 6421: 6284: 6105: 3117: 3070: 3062: 2878:

causes considerable demethylation of 5-mCpG sites, shorter times of H

2785: 1846: 1696: 1624: 1593: 1543: 1536: 1483: 1445: 1252: 1213: 1189: 1102: 1045: 979: 921: 771: 705: 633: 617: 569: 301: 290: 286: 272: 239: 119: 93: 69: 9140: 8186: 7115:"Mutator pathways unleashed by epigenetic silencing in human cancer" 6985: 6863:"DNA damage response genes and the development of cancer metastasis" 6728: 6223: 5616:"The role of the cyclin-dependent kinase inhibitor p21 in apoptosis" 5479: 5271: 3627: 903:

bond between the phosphate backbone and the deoxyribose nucleotides.

410:(e.g., benzopyrene diol epoxide-dG adduct, aristolactam I-dA adduct) 179:

for their work on the molecular mechanisms of DNA repair processes.

143:

have turned out to be involved in DNA damage repair and protection.

10687: 10560: 9486: 8140:"MicroRNA-182-5p targets a network of genes involved in DNA repair" 7838: 6562:"DNA repair, genome stability and cancer: a historical perspective" 5851:"Premature aging in mice deficient in DNA repair and transcription" 4755: 3172: 3097: 3058: 3005: 2957: 2820: 2781: 2762: 2726: 2718: 2564: 2480: 1942: 1934: 1896:

Inherited human DNA repair gene mutations that increase cancer risk

1874:

Other diseases associated with reduced DNA repair function include

1864: 1850: 1671: 1574: 1383: 1375: 1287:, a component of the nucleosome remodeling and deacetylase complex 1192:. The common features of global response are induction of multiple 1140: 1105:

and the second adenine will be added in its syn conformation using

746: 737:, whose activation is obligately dependent on energy absorbed from 645: 609: 585: 461: 440: 435: 423:

Monoadduct damage cause by change in single nitrogenous base of DNA

326: 85: 72:

can cause DNA damage, resulting in tens of thousands of individual

7743: 5799: 5231:

Rogakou EP, Pilch DR, Orr AH, Ivanova VS, Bonner WM (March 1998).

4156: 4131: 3822:(5th ed.). Pearson Benjamin Cummings; CSHL Press. Ch. 9, 10. 2529: 1359:, initiating its function, about 10 minutes after DNA is damaged. 733:

process directly reverses this damage by the action of the enzyme

10507: 10259: 9141:

D'Augustin O, Huet S, Campalans A, Radicella JP (November 2020).

7654:

Halford S, Rowan A, Sawyer E, Talbot I, Tomlinson I (June 2005).

7063: 6326:

If we lived long enough, sooner or later we all would get cancer.

4377:"Biochemical evidence for Ku-independent backup pathways of NHEJ" 3818:

Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R (2004).

2568: 1585:, SOS boxes are 20-nucleotide long sequences near promoters with 1391: 1387: 1379: 1275: 1169: 1069: 1018:. Partially overlapping fragments are then used for synthesis of 816: 754: 629: 444: 322: 243: 227: 89: 9923:"CRISPR gene-editing tool has scientists thrilled – but nervous" 8451: 7967:"Modulation of mismatch repair and genomic stability by miR-155" 2819:

When OGG1 is present at an oxidized guanine within a methylated

2796:(8-OHdG), and resulting in a 5mCp-8-OHdG dinucleotide site. The 628:

Senescence, an irreversible process in which the cell no longer

128:

unregulated cell division, which can lead to the formation of a

10632: 10387: 10340: 10335: 10032: 9548: 8077:, 15 April 2014, MD Anderson Cancer Center, University of Texas 7510: 7205: 6663: 6221: 5320: 4576: 4468:"Unraveling V(D)J recombination; insights into gene regulation" 4042: 3083: 3066: 3049:. The mechanism by which this came about, however, is unclear. 1729:

Most life span influencing genes affect the rate of DNA damage.

1661: 1494: 1395: 1344: 1264: 1133: 1023: 763: 701: 657: 511: 499: 223: 133: 97: 61: 10061:"Human DNA repair diseases: From genome instability to cancer" 9334: 6918:

Zhang P, Wang J, Gao W, Yuan BZ, Rogers J, Reed E (May 2004).

5848: 4628:"Alternative end-joining mechanisms: a historical perspective" 2914:(BER) of oxidative damage occurred with the DNA repair enzyme 1665:

DNA repair rate is an important determinant of cell pathology.

41: 10647: 10642: 10637: 10627: 10620: 10615: 10610: 10605: 10600: 10590: 10585: 10440: 10404: 10325: 10320: 10315: 10305: 10208: 7206:

Bernstein C, Nfonsam V, Prasad AR, Bernstein H (March 2013).

5372: 5026: 4132:"Yeast DNA ligase IV mediates non-homologous DNA end joining" 3187: 3001: 2927: 2812:

Oxidized guanine has mispairing potential and is mutagenic.

2705:

Genome-wide distribution of DNA repair in human somatic cells

2630: 2626: 2617: 2611: 2579: 2575: 2476: 2472: 2339: 2182: 2151: 1930: 1910: 1904: 1691: 1683: 1606: 1427: 1419: 1356: 1318: 1310: 1306: 1271: 1259: 1248: 1240: 1177: 1137: 963: 955: 951: 917: 900: 895: 750: 745:) to promote catalysis. Photolyase, an old enzyme present in 696:

DNA damage (naturally occurring) § Repair of damaged DNA

335: 316: 313: 297: 207: 129: 9489:"Recruitment of DNA methyltransferase I to DNA repair sites" 8852: 7964: 7923: 7364: 7256: 5964: 5905: 5647:"Some aspects of the SOS response system--a critical survey" 3613: 3447: 2697:

pathway are also over-expressed in a number of cancers (see

1859:: sensitivity to ionizing radiation and some chemical agents 1725: 1523:

and other bacteria in response to extensive DNA damage. The

159:

Paul Modrich talks about himself and his work in DNA repair.

10533: 10489: 10484: 10419: 10414: 10409: 10382: 10362: 10357: 10310: 9756: 9551:"DNA damage, homology-directed repair, and DNA methylation" 8953: 8401: 7513:"DNA damage, homology-directed repair, and DNA methylation" 7315: 6714: 6185: 5080: 3037:

organisms, as well as the presence of potentially damaging

2944:

Homologous recombinational repair alters epigenetic markers

2750:

Repair of oxidative DNA damage can alter epigenetic markers

2736: 2686: 2560: 2556: 1758:

induced by endogenously generated reactive oxygen species.

1747: 1703:

carcinogens and correspondingly increased cancer risk (see

1532: 1528: 1423: 1298: 1294: 1284: 1280: 1193: 1109:. From a cellular perspective, risking the introduction of 1094: 1082: 1031: 967: 909: 81: 6765: 5184: 4676: 3958:. Methods in Enzymology. Vol. 408. pp. 189–213. 3488: 3250: 2450: 1656: 10295: 10290: 8137: 7459: 6609: 6470: 6270: 5132: 1490: 1479: 1449: 1181: 231: 57: 8023: 7653: 6134: 5465: 5416: 3896: 3387: 1950:

pathways and reversion of previously inhibited defects.

1634:, homologous recombination, nucleotide excision repair, 5758: 5729: 1704: 1455:

Checkpoint Proteins can be separated into four groups:

10155: 9648: 9191: 8500: 5230: 2729:-marked regions. Another important mechanism concerns 1863:

All of the above diseases are often called "segmental

10676: 9705: 9383: 9002: 8703: 4804: 4374: 4129: 2586:

the 5 types of DNA damages illustrated in the chart.

1790: 1325:

pathway to enter the chromatin and repair UV-induced

226:

that do not fit in the standard double helix. Unlike

10115:"DNA-damage repair; the good, the bad, and the ugly" 9435: 8901: 3283: 3093: 1754:, and concurrently to reduce constitutive level of 1720: 1448:

and slows down the rate of S phase progression when

1010:

has a remarkable ability to survive DNA damage from

576:

and is condensed into aggregate structures known as

197:

DNA damage, due to environmental factors and normal

9805: 7702: 7208:"Epigenetic field defects in progression to cancer" 6338:Alberts B, Johnson A, Lewis J, et al. (2002). 6337: 5368: 5366: 4980:"Chromatin remodeling, DNA damage repair and aging" 4091:"Modulation of DNA end joining by nuclear proteins" 3999:. New York: W.H. Freeman and Company. p. 840. 3817: 1119:the toxicity and mutagenesis of the same lesion in 1077:post-translational modification of the replication 279:exogenous damage caused by external agents such as 45:

DNA damage resulting in multiple broken chromosomes

9806:Cromie GA, Connelly JC, Leach DR (December 2001). 7460:O'Hagan HM, Mohammad HP, Baylin SB (August 2008). 7156:"Epigenetic changes of DNA repair genes in cancer" 6816: 6083: 5586: 3994: 3213: 1801: 1594:Eukaryotic transcriptional responses to DNA damage 1136:, PCNA is ubiquitinated, or modified, by the RAD6/ 254:DNA damage can be subdivided into two main types: 10044:Roswell Park Cancer Institute DNA Repair Lectures 6860: 4805:Colis LC, Raychaudhury P, Basu AK (August 2008). 4278: 2948:At least four articles report the recruitment of 2926:region and the early transcription region of the 1478:An important downstream target of ATM and ATR is 1144:a specialized polymerase is needed to extend it; 1089:mediates error-free bypass of lesions induced by 10700: 9250: 9056: 7195:Epigenetic changes of DNA repair genes in cancer 6917: 6819:"Nucleotide excision repair and human syndromes" 6034: 5688: 5363: 4853: 4517: 3763: 1565:or double-strand breaks, which are processed by 1550:sequences commonly referred to as SOS boxes. In 1151: 1064:machinery to replicate past DNA lesions such as 616:, which is present in both the mitochondria and 510:at 40–80 °C. The rate of depurination (300 481:such as that created by radioactive decay or in 293:) from the sun or other artificial light sources 9925:CBC news. Author Kelly Crowe. 30 November 2015. 9888:The Anatomical Record Part B: The New Anatomist 9881: 9599: 8276: 7112: 6521: 5764: 5508: 5226: 5224: 5222: 4180: 4130:Wilson TE, Grawunder U, Lieber MR (July 1997). 4088: 4084: 4082: 3664:"Nuclear DNA damage as a direct cause of aging" 3322: 2530:Frequencies of epimutations in DNA repair genes 1953: 1845:: sunlight hypersensitivity, high incidence of 1504: 833:(NER): bulky, helix-distorting damage, such as 757:no longer functions in humans, who instead use 636:. The telomeres are long regions of repetitive 551: 469:. The damage caused by free radicals is called 10049:A comprehensive list of Human DNA Repair Genes 8752: 8699: 8697: 8227: 7455: 7453: 7451: 6559: 4235: 3422: 3052: 2952:to sites of DNA double-strand breaks. During 494:at elevated temperature increases the rate of 10224: 9750: 9699: 9642: 9593: 9480: 9377: 9328: 9279: 9244: 9185: 9134: 9085: 8996: 8895: 8586: 8535: 8494: 8445: 8395: 8354: 8319: 8313: 8270: 8080: 7794: 6659: 6657: 6555: 6553: 5950: 5948: 5946: 3953: 2984:The basic processes of DNA repair are highly 2725:proteins, thereby lowering mutation rates in 2714:. One mechanism underlying this involves the 1527:SOS system is regulated by two key proteins: 1267:, to initiate DNA repair, within 13 seconds. 982:(available in G2 after DNA replication) or a 791:Structure of the base-excision repair enzyme 242:and wound around "packaging" proteins called 68:activities and environmental factors such as 10058: 8949: 8947: 8086: 7153: 6560:Jeggo PA, Pearl LH, Carr AM (January 2016). 6364: 5689:Erill I, Campoy S, Barbé J (November 2007). 5459: 5314: 5265: 5219: 4847: 4798: 4749: 4625: 4619: 4570: 4284: 4079: 3607: 3537: 2602:DNA repair pathways appear to be central to 1819:: hypersensitivity to UV and chemical agents 990:and are typically repaired by recombination. 872:The main double-strand break repair pathways 217:The vast majority of DNA damage affects the 112:an irreversible state of dormancy, known as 9846: 8801: 8694: 8643: 8367:International Journal of Molecular Medicine 8360: 7448: 7014: 6861:Broustas CG, Lieberman HB (February 2014). 6346:(4th ed.). 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This complex further complexes with the 623: 600:, byproducts of the constant production of 10231: 10217: 9544: 9542: 9285: 7212:World Journal of Gastrointestinal Oncology 6654: 6550: 6370: 6077: 5943: 4977: 4762:Microbiology and Molecular Biology Reviews 4451:|...|intentional=yes}} 4186: 4045:Journal of the American Geriatrics Society 3949: 3947: 3945: 3943: 3350: 2765:(a cytosine followed by guanine along its 2701:for summary), and are also shown in cyan. 2658: 2595: 928:, the process that generates diversity in 709: 10247: 10191: 10181: 10138: 10076: 9899: 9823: 9782: 9733: 9723: 9682: 9625: 9576: 9566: 9522: 9512: 9463: 9453: 9431: 9429: 9409: 9360: 9311: 9227: 9217: 9168: 9158: 9117: 9028: 8979: 8944: 8927: 8878: 8829: 8819: 8778: 8729: 8677: 8620: 8610: 8569: 8559: 8518: 8477: 8378: 8337: 8253: 8204: 8163: 8114: 8051: 8041: 8000: 7990: 7941: 7856: 7771: 7761: 7720: 7679: 7587: 7538: 7528: 7487: 7477: 7431: 7390: 7341: 7292: 7282: 7233: 7223: 7179: 7130: 7089: 7040: 6968: 6945: 6935: 6894: 6837: 6447: 6398: 6388: 6239: 6060: 5958: 5874: 5825: 5706: 5662: 5584: 5559: 5442: 5390: 5346: 5289: 5248: 5202: 5180: 5178: 5158: 5106: 5076: 5074: 5072: 5052: 5003: 4879: 4830: 4781: 4653: 4643: 4602: 4553: 4543: 4513: 4511: 4483: 4400: 4351: 4325: 4302: 4261: 4236:Boulton SJ, Jackson SP (September 1996). 4212: 4155: 4106: 4036: 4022:Johns Hopkins Medical Journal. 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The 1444:progression in G1, G2 and 1323:nucleotide excision repair 1200:arrest, and inhibition of 882:non-homologous end joining 831:Nucleotide excision repair 759:nucleotide excision repair 693: 329:compounds that act as DNA 249: 193:Free radical damage to DNA 186: 60:molecules that encode its 31: 10656: 10521: 10500: 10428: 10373: 10246: 10113:Hakem R (February 2008). 10103:DNA Damage and DNA Repair 9958:Resources in your library 9775:10.18632/oncotarget.16122 8234:Molecular Cancer Research 7895:10.1007/s11033-012-2465-3 7883:Molecular Biology Reports 7810:10.1007/s00423-011-0812-9 6524:Annual Review of Medicine 6006:10.1016/j.mad.2005.03.016 5695:FEMS Microbiology Reviews 3113:Accelerated aging disease 3043:oxidative phosphorylation 1889: 1230:histone-modifying enzymes 1103:Watson-Crick base pairing 1022:regions through a moving 606:oxidative phosphorylation 261:damage such as attack by 10453:Homology directed repair 10375:Homologous recombination 10096:12 February 2018 at the 9493:Proc Natl Acad Sci U S A 9198:Proc Natl Acad Sci U S A 8326:Clinical Cancer Research 7845:Clinical Cancer Research 7763:10.3748/wjg.v16.i28.3553 7580:10.1177/1947601911413466 5818:10.1038/sj.embor.7400127 5651:Acta Biochimica Polonica 4732:2003 Apr;159(4):502–10. 4645:10.3389/fgene.2013.00048 4583:Cell Death & Disease 4344:10.1038/sj.emboj.7600563 4304:10.1074/jbc.274.33.23599 3997:Biochemistry 7th edition 3357:Staff (7 October 2015). 2479:) and changes caused by 1939:homologous recombination 1645: 1611:Saccharomyces cerevisiae 1414:downstream targets in a 1036:homologous recombination 890:homologous recombination 624:Senescence and apoptosis 408:"bulky adduct formation" 381:), such as formation of 355: 165:Nobel Prize in Chemistry 9514:10.1073/pnas.0501034102 9292:Neuropsychopharmacology 9219:10.1073/pnas.0406048101 8612:10.1186/1471-2407-13-90 7992:10.1073/pnas.1002472107 7672:10.1136/gut.2004.059535 7562:Malkin D (April 2011). 7414:German J (March 1969). 6839:10.1093/carcin/21.3.453 6788:10.1126/science.1140735 6390:10.1186/1471-2407-7-152 6157:10.1126/science.1099196 5876:10.1126/science.1070174 5379:Journal of Cell Science 5250:10.1074/jbc.273.10.5858 5099:10.1091/mbc.E16-05-0269 4904:"Translesion Synthesis" 4626:Decottignies A (2013). 4545:10.1073/pnas.1213431110 3899:Prescott's Microbiology 3192:The scientific journal 2756:8-oxo-2'-deoxyguanosine 2548:in the DNA repair gene 1742:pathways and decreased 1710:Deinococcus radiodurans 1499:cyclin-dependent kinase 1007:Deinococcus radiodurans 835:pyrimidine dimerization 671:8-hydroxydeoxyguanosine 594:reactive oxygen species 404:, and depyrimidination. 348:, for example, through 263:reactive oxygen species 10475:Postreplication repair 10270:Uracil-DNA glycosylase 9993: 9973:Listen to this article 8972:10.1093/nar/29.10.2117 8520:10.1038/sj.onc.1206977 8380:10.3892/ijmm.2014.1682 8156:10.1261/rna.034926.112 8075:Human DNA Repair Genes 7564:"Li-fraumeni syndrome" 7284:10.1073/pnas.94.7.3122 6974:Nature Reviews. 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An intra- 1056:Translesion synthesis 984:homologous chromosome 976:chromosomal crossover 898: 878:genome rearrangements 871: 790: 710:translesion synthesis 620:of eukaryotic cells. 540:, just to name a few. 504:thermophilic bacteria 309:or thermal disruption 267:oxidative deamination 187:Further information: 158: 124:programmed cell death 44: 32:For the journal, see 10581:core protein complex 10256:Base excision repair 10040:at Wikimedia Commons 10024:More spoken articles 9455:10.3390/cells9010225 9304:10.1038/npp.2012.112 9160:10.3390/ijms21218360 8914:(Suppl 1): S130–45. 8859:Nature Biotechnology 8206:10.1038/onc.2011.660 5967:Uchu Seibutsu Kagaku 5564:. World Scientific. 5045:10.4161/cc.8.14.8984 3581:DNA and Cell Biology 3507:10.4161/cc.5.17.3191 3475:10.3123/jemsge.28.56 2912:Base excision repair 2798:base excision repair 2721:, which can recruit 2716:histone modification 2469:histone modification 1978:Li-Fraumeni syndrome 1334:chromatin remodeling 1226:chromatin remodeling 864:Double-strand breaks 809:Base excision repair 783:Single-strand damage 614:superoxide dismutase 612:of these species is 556:In human cells, and 522:Industrial chemicals 518:cannot be ruled out. 331:intercalating agents 234:, DNA usually lacks 34:DNA Repair (journal) 10353:DNA mismatch repair 10174:2016PLoSO..1151367M 9769:(25): 40359–40372. 9667:2016NatSR...633222R 9505:2005PNAS..102.8905M 9402:10.1093/jmcb/mjv050 9210:2004PNAS..10113738L 9092:Poetsch AR (2020). 8670:10.1038/nature14173 8662:2015Natur.521...81S 8561:10.1155/2013/946268 7983:2010PNAS..107.6982V 7722:10.1093/jnci/dji275 7625:1997Sci...278.1043F 7275:1997PNAS...94.3122N 7172:10.1093/jmcb/mjq053 6879:2014RadR..181..111B 6780:2008Sci...319.1352H 6686:10.1038/nature05268 6678:2006Natur.444..633B 6632:10.1038/nature03482 6624:2005Natur.434..864B 6493:10.1038/nature03443 6485:2005Natur.434..913B 6149:2004Sci...305..390C 6098:2001Natur.410..227T 5921:2006MRFMM.596...22D 5867:2002Sci...296.1276D 5531:10.1038/nature01368 5523:2003Natur.421..499B 5468:Nature Cell Biology 4699:10.1038/nature05160 4691:2006Natur.443..569Z 4536:2013PNAS..110.7720T 4426:10.1093/nar/gkaa228 4148:1997Natur.388..495W 3855:1988EnvMM..11..241V 3710:on 15 November 2017 3466:2006GeneE..28...56O 3163:Indirect DNA damage 3041:in the cell due to 2621:, are required for 2505:DNA mismatch repair 2447: 1823:Trichothiodystrophy 1736:Caloric restriction 1416:signal transduction 926:V(D)J recombination 538:crosslinking of DNA 471:indirect DNA damage 385:, 1-methyladenine, 323:mutagenic chemicals 212:tumor heterogeneity 18:Double-strand break 10719:Molecular genetics 10714:Cellular processes 10108:Segmental Progeria 9994: 9901:10.1002/ar.b.20089 9618:10.1093/hmg/ddq451 8814:(3): 534–547.e23. 8332:(2 Pt 1): 473–82. 7568:Genes & Cancer 6867:Radiation Research 6581:10.1038/nrc.2015.4 6321:The New York Times 5955:PMID 26729707 5392:10.1242/jcs.008367 5385:(Pt 15): 2706–16. 4393:10.1093/nar/gkg728 3956:DNA Repair, Part A 3922:Russell P (2018). 3336:The New York Times 3031:oxygen catastrophe 2908:potassium chromate 2810: 2541: 2524:germline mutations 2442: 1961:Replication stress 1752:metabolic activity 1731: 1680:maximum life spans 1667: 1513:is the changes in 1367:After DNA damage, 1220:. In eukaryotes, 1158:ionizing radiation 1012:ionizing radiation 905: 874: 819:). Enzymes called 797: 712:as a last resort. 654:cellular signaling 492:Thermal disruption 478:Ionizing radiation 396:of bases, such as 377:of bases (usually 273:replication errors 236:tertiary structure 161: 102:two-hit hypothesis 47: 27:Cellular mechanism 10674: 10673: 10549:Adaptive response 10036:Media related to 9990: 9939:Library resources 9861:10.1021/cr040481v 9675:10.1038/srep33222 9021:10.1021/ja411636j 8960:Nucleic Acids Res 8279:BJU International 8106:978-1-4419-9966-5 7619:(5340): 1043–50. 7021:Clinical Genetics 6887:10.1667/RR13515.1 6774:(5868): 1352–55. 6353:978-0-8153-4072-0 5909:Mutation Research 5861:(5571): 1276–79. 5744:10.1021/cr0404951 5645:Janion C (2001). 5600:978-1-58829-500-2 5571:978-981-270-014-8 5517:(6922): 499–506. 4931:Mutation Research 4872:10.1021/bi102064z 4823:10.1021/bi800529f 4297:(33): 23599–609. 4006:978-1-4292-2936-4 3973:978-0-12-182813-4 3933:978-93-325-7162-4 3908:978-0-07-340240-6 3743:10.1021/cr0204348 3434:978-0-13-196893-6 3262:978-0-7167-4366-8 3199:Mutation Research 3143:Direct DNA damage 3010:structural motifs 2904:potassium bromate 2778:DNA demethylation 2767:5' → 3' direction 2710:late-replicating 2546:missense mutation 2448: 2441: 1970:short hairpin RNA 1837:Werner's syndrome 1817:Cockayne syndrome 1563:replication forks 1408:replication forks 1239:, phosphorylates 1186:replication forks 1162:ultraviolet light 1156:Cells exposed to 776:adaptive response 741:(300–500 nm 731:photoreactivation 727:pyrimidine dimers 530:hydrogen peroxide 516:adaptive response 455:direct DNA damage 453:. This is called 450:pyrimidine dimers 387:6-O-Methylguanine 383:7-methylguanosine 219:primary structure 156: 74:molecular lesions 16:(Redirected from 10736: 10691: 10690: 10682: 10664: 10663: 10233: 10226: 10219: 10210: 10209: 10205: 10195: 10185: 10152: 10142: 10082: 10080: 10035: 10014: 10012: 10001: 10000: 9991: 9981: 9979: 9974: 9926: 9920: 9914: 9913: 9903: 9879: 9873: 9872: 9849:Chemical Reviews 9844: 9838: 9837: 9827: 9803: 9797: 9796: 9786: 9754: 9748: 9747: 9737: 9727: 9703: 9697: 9696: 9686: 9646: 9640: 9639: 9629: 9597: 9591: 9590: 9580: 9570: 9546: 9537: 9536: 9526: 9516: 9484: 9478: 9477: 9467: 9457: 9433: 9424: 9423: 9413: 9381: 9375: 9374: 9364: 9353:10.1038/nbt.2726 9332: 9326: 9325: 9315: 9283: 9277: 9276: 9259:(9): 1163–1171. 9248: 9242: 9241: 9231: 9221: 9204:(38): 13738–43. 9189: 9183: 9182: 9172: 9162: 9138: 9132: 9131: 9121: 9089: 9083: 9082: 9065:(9): 1163–1171. 9054: 9043: 9042: 9032: 9000: 8994: 8993: 8983: 8951: 8942: 8941: 8931: 8899: 8893: 8892: 8882: 8871:10.1038/nbt.2778 8850: 8844: 8843: 8833: 8823: 8799: 8793: 8792: 8782: 8750: 8744: 8743: 8733: 8701: 8692: 8691: 8681: 8641: 8635: 8634: 8624: 8614: 8590: 8584: 8583: 8573: 8563: 8539: 8533: 8532: 8522: 8498: 8492: 8491: 8481: 8449: 8443: 8442: 8408: 8399: 8393: 8392: 8382: 8358: 8352: 8351: 8341: 8317: 8311: 8310: 8274: 8268: 8267: 8257: 8225: 8219: 8218: 8208: 8184: 8178: 8177: 8167: 8135: 8129: 8128: 8118: 8084: 8078: 8072: 8066: 8065: 8055: 8045: 8030:Genome Integrity 8021: 8015: 8014: 8004: 7994: 7962: 7956: 7955: 7945: 7930:Gastroenterology 7921: 7915: 7914: 7877: 7871: 7870: 7860: 7836: 7830: 7829: 7792: 7786: 7785: 7775: 7765: 7741: 7735: 7734: 7724: 7700: 7694: 7693: 7683: 7651: 7645: 7644: 7608: 7602: 7601: 7591: 7559: 7553: 7552: 7542: 7532: 7508: 7502: 7501: 7491: 7481: 7457: 7446: 7445: 7435: 7411: 7405: 7404: 7394: 7362: 7356: 7355: 7345: 7313: 7307: 7306: 7296: 7286: 7254: 7248: 7247: 7237: 7227: 7203: 7197: 7193: 7183: 7151: 7145: 7144: 7134: 7110: 7104: 7103: 7093: 7061: 7055: 7054: 7044: 7012: 7006: 7005: 6966: 6960: 6959: 6949: 6939: 6924:Molecular Cancer 6915: 6909: 6908: 6898: 6858: 6852: 6851: 6841: 6823: 6814: 6808: 6807: 6763: 6757: 6756: 6712: 6706: 6705: 6672:(7119): 633–37. 6661: 6652: 6651: 6618:(7035): 864–70. 6607: 6601: 6600: 6566: 6557: 6548: 6547: 6519: 6513: 6512: 6479:(7035): 913–17. 6468: 6462: 6461: 6451: 6419: 6413: 6412: 6402: 6392: 6368: 6362: 6361: 6335: 6329: 6328: 6311: 6305: 6304: 6285:10.1038/35012693 6279:(6784): 296–97. 6268: 6262: 6261: 6243: 6219: 6213: 6212: 6183: 6177: 6176: 6143:(5682): 390–92. 6132: 6126: 6125: 6106:10.1038/35065638 6092:(6825): 227–30. 6081: 6075: 6074: 6064: 6032: 6026: 6025: 5989: 5983: 5982: 5962: 5956: 5952: 5941: 5940: 5903: 5897: 5896: 5878: 5846: 5840: 5839: 5829: 5797: 5791: 5790: 5762: 5756: 5755: 5732:Chemical Reviews 5727: 5721: 5720: 5710: 5686: 5677: 5676: 5666: 5642: 5636: 5635: 5611: 5605: 5604: 5593:. Humana Press. 5592: 5582: 5576: 5575: 5557: 5551: 5550: 5506: 5500: 5499: 5463: 5457: 5456: 5446: 5414: 5405: 5404: 5394: 5370: 5361: 5360: 5350: 5327:The EMBO Journal 5318: 5312: 5311: 5293: 5269: 5263: 5262: 5252: 5228: 5217: 5216: 5206: 5182: 5173: 5172: 5162: 5130: 5121: 5120: 5110: 5078: 5067: 5066: 5056: 5024: 5018: 5017: 5007: 4984:Current Genomics 4975: 4969: 4966: 4955: 4954: 4926: 4920: 4919: 4917: 4915: 4910:on 10 March 2012 4900: 4894: 4893: 4883: 4851: 4845: 4844: 4834: 4802: 4796: 4795: 4785: 4753: 4747: 4725: 4719: 4718: 4685:(7111): 569–73. 4674: 4668: 4667: 4657: 4647: 4623: 4617: 4616: 4606: 4574: 4568: 4567: 4557: 4547: 4515: 4506: 4505: 4487: 4463: 4457: 4456: 4454: 4452: 4444: 4414: 4404: 4372: 4366: 4365: 4355: 4332:The EMBO Journal 4323: 4317: 4316: 4306: 4282: 4276: 4275: 4265: 4248:(18): 5093–103. 4242:The EMBO Journal 4233: 4227: 4226: 4216: 4184: 4178: 4177: 4159: 4127: 4121: 4120: 4110: 4101:(36): 31442–49. 4086: 4077: 4076: 4040: 4034: 4033: 4017: 4011: 4010: 3992: 3986: 3985: 3951: 3938: 3937: 3919: 3913: 3912: 3894: 3883: 3882: 3838: 3832: 3831: 3815: 3804: 3803: 3793: 3761: 3755: 3754: 3731:Chemical Reviews 3726: 3720: 3719: 3717: 3715: 3709: 3703:. Archived from 3686: 3668: 3659: 3648: 3647: 3611: 3605: 3604: 3576: 3570: 3569: 3559: 3535: 3529: 3528: 3518: 3486: 3480: 3479: 3477: 3445: 3439: 3438: 3420: 3414: 3413: 3385: 3379: 3378: 3376: 3374: 3363: 3354: 3348: 3347: 3345: 3343: 3326: 3320: 3319: 3301: 3281: 3275: 3274: 3248: 3239: 3238: 3236: 3234: 3217: 3106: 3101: 3100: 3047:oxidative stress 2790:5-methylcytosine 2544:only four had a 2446: 2438: 2437: 2425: 2424: 2416: 2415: 2402: 2401: 2393: 2392: 2386: 2385: 2377: 2376: 2361: 2360: 2350: 2349: 2334: 2333: 2327: 2326: 2320: 2319: 2298: 2297: 2291: 2290: 2269: 2268: 2262: 2261: 2249: 2248: 2231: 2230: 2220: 2219: 2202: 2201: 2191: 2190: 2171: 2170: 2160: 2159: 2144: 2143: 2133: 2132: 2124: 2123: 2102: 2101: 2095: 2094: 2075: 2074: 2068: 2067: 2061: 2060: 2041: 2040: 2034: 2033: 2027: 2026: 1992: 1991: 1843:Bloom's syndrome 1740:nutrient sensing 1583:Escherichia coli 1553:Escherichia coli 1520:Escherichia coli 1410:. These kinases 1303:ubiquitin ligase 1121:Escherichia coli 988:replication fork 934:T-cell receptors 912:, a specialized 821:AP endonucleases 644:). In contrast, 506:, which grow in 426:Di adduct damage 157: 21: 10744: 10743: 10739: 10738: 10737: 10735: 10734: 10733: 10699: 10698: 10697: 10685: 10677: 10675: 10670: 10652: 10522:Other/ungrouped 10517: 10496: 10424: 10369: 10265:DNA glycosylase 10248:Excision repair 10242: 10237: 10168:(3): e0151367. 10098:Wayback Machine 10028: 10027: 10016: 10010: 10008: 10005:This audio file 10002: 9995: 9986: 9983: 9977: 9976: 9972: 9969: 9968: 9967: 9947: 9946: 9942: 9935: 9930: 9929: 9921: 9917: 9880: 9876: 9845: 9841: 9804: 9800: 9755: 9751: 9704: 9700: 9647: 9643: 9598: 9594: 9547: 9540: 9485: 9481: 9434: 9427: 9390:J Mol Cell Biol 9382: 9378: 9347:(12): 1137–42. 9341:Nat. Biotechnol 9333: 9329: 9284: 9280: 9249: 9245: 9190: 9186: 9139: 9135: 9090: 9086: 9055: 9046: 9015:(11): 4223–35. 9001: 8997: 8966:(10): 2117–26. 8952: 8945: 8900: 8896: 8851: 8847: 8800: 8796: 8751: 8747: 8702: 8695: 8656:(7550): 81–84. 8642: 8638: 8591: 8587: 8540: 8536: 8513:(46): 7243–46. 8499: 8495: 8450: 8446: 8406: 8400: 8396: 8359: 8355: 8318: 8314: 8275: 8271: 8240:(11): 1710–17. 8226: 8222: 8199:(49): 5108–16. 8185: 8181: 8136: 8132: 8107: 8085: 8081: 8073: 8069: 8022: 8018: 7977:(15): 6982–87. 7963: 7959: 7922: 7918: 7878: 7874: 7837: 7833: 7793: 7789: 7756:(28): 3553–60. 7742: 7738: 7715:(18): 1330–38. 7701: 7697: 7652: 7648: 7609: 7605: 7560: 7556: 7509: 7505: 7472:(8): e1000155. 7458: 7449: 7412: 7408: 7363: 7359: 7328:(12): 2402–08. 7314: 7310: 7255: 7251: 7204: 7200: 7152: 7148: 7111: 7107: 7062: 7058: 7013: 7009: 6986:10.1038/nrc1799 6967: 6963: 6916: 6912: 6859: 6855: 6821: 6815: 6811: 6764: 6760: 6729:10.1038/nrc3916 6713: 6709: 6662: 6655: 6608: 6604: 6564: 6558: 6551: 6520: 6516: 6469: 6465: 6420: 6416: 6369: 6365: 6354: 6336: 6332: 6312: 6308: 6269: 6265: 6220: 6216: 6184: 6180: 6133: 6129: 6082: 6078: 6033: 6029: 5990: 5986: 5963: 5959: 5953: 5944: 5904: 5900: 5847: 5843: 5798: 5794: 5763: 5759: 5728: 5724: 5687: 5680: 5643: 5639: 5612: 5608: 5601: 5583: 5579: 5572: 5558: 5554: 5507: 5503: 5480:10.1038/ncb1337 5464: 5460: 5415: 5408: 5371: 5364: 5333:(11): 2511–27. 5319: 5315: 5270: 5266: 5243:(10): 5858–68. 5229: 5220: 5197:(2): 1197–208. 5183: 5176: 5145:(10): 2641–50. 5131: 5124: 5079: 5070: 5025: 5021: 4976: 4972: 4967: 4958: 4927: 4923: 4913: 4911: 4902: 4901: 4897: 4852: 4848: 4803: 4799: 4754: 4750: 4726: 4722: 4675: 4671: 4624: 4620: 4575: 4571: 4516: 4509: 4464: 4460: 4446: 4438: 4436: 4415: 4387:(18): 5377–88. 4373: 4369: 4324: 4320: 4283: 4279: 4234: 4230: 4185: 4181: 4142:(6641): 495–8. 4128: 4124: 4087: 4080: 4041: 4037: 4018: 4014: 4007: 3993: 3989: 3974: 3952: 3941: 3934: 3920: 3916: 3909: 3895: 3886: 3839: 3835: 3816: 3807: 3762: 3758: 3727: 3723: 3713: 3711: 3707: 3666: 3660: 3651: 3628:10.1038/nrm2233 3612: 3608: 3577: 3573: 3544:Cancer Research 3536: 3532: 3501:(17): 1940–45. 3487: 3483: 3446: 3442: 3435: 3421: 3417: 3386: 3382: 3372: 3370: 3361: 3355: 3351: 3341: 3339: 3327: 3323: 3299:10.1.1.556.6874 3282: 3278: 3263: 3249: 3242: 3232: 3230: 3219: 3218: 3214: 3209: 3204: 3138:DNA replication 3102: 3095: 3092: 3080: 3055: 2996:and even among 2982: 2971: 2946: 2916:polymerase beta 2893: 2889: 2885: 2881: 2877: 2873: 2867:messenger RNA. 2849: 2845: 2837: 2833: 2752: 2739: 2723:mismatch repair 2712:heterochromatin 2707: 2532: 2465:DNA methylation 2453: 2443: 1956: 1892: 1882:and hereditary 1804: 1799: 1793: 1723: 1688:naked mole-rats 1659: 1654: 1648: 1596: 1541:transcriptional 1515:gene expression 1507: 1365: 1210: 1154: 1111:point mutations 1074:DNA polymerases 1062:DNA replication 1058: 866: 849:Mismatch repair 802:excision repair 785: 722: 720:Direct reversal 698: 692: 666: 626: 564:and inside the 554: 465:creates mostly 447:bases creating 418:DNA replication 358: 350:gene conversion 252: 195: 185: 167:was awarded to 146: 37: 28: 23: 22: 15: 12: 11: 5: 10742: 10732: 10731: 10726: 10721: 10716: 10711: 10696: 10695: 10672: 10671: 10669: 10668: 10657: 10654: 10653: 10651: 10650: 10645: 10640: 10635: 10630: 10625: 10624: 10623: 10618: 10613: 10608: 10603: 10598: 10593: 10588: 10573: 10572: 10567: 10557: 10556: 10551: 10546: 10541: 10536: 10531: 10525: 10523: 10519: 10518: 10516: 10515: 10510: 10504: 10502: 10498: 10497: 10495: 10494: 10493: 10492: 10487: 10477: 10472: 10467: 10466: 10465: 10455: 10450: 10449: 10448: 10443: 10432: 10430: 10429:Other pathways 10426: 10425: 10423: 10422: 10417: 10412: 10407: 10402: 10401: 10400: 10390: 10385: 10379: 10377: 10371: 10370: 10368: 10367: 10366: 10365: 10360: 10350: 10349: 10348: 10343: 10338: 10333: 10328: 10323: 10318: 10313: 10308: 10303: 10298: 10293: 10279: 10278: 10277: 10272: 10267: 10252: 10250: 10244: 10243: 10236: 10235: 10228: 10221: 10213: 10207: 10206: 10153: 10125:(4): 589–605. 10110: 10105: 10100: 10088: 10083: 10071:(4): 755–762. 10065:Braz. J. Genet 10056: 10051: 10046: 10041: 10017: 10003: 9996: 9984: 9971: 9970: 9966: 9965: 9960: 9955: 9949: 9948: 9937: 9936: 9934: 9933:External links 9931: 9928: 9927: 9915: 9874: 9839: 9818:(6): 1163–74. 9812:Molecular Cell 9798: 9749: 9698: 9641: 9592: 9538: 9499:(25): 8905–9. 9479: 9425: 9376: 9327: 9278: 9243: 9184: 9133: 9084: 9044: 8995: 8943: 8894: 8845: 8794: 8765:(3): 590–600. 8745: 8716:(4): 1228–34. 8693: 8636: 8585: 8534: 8493: 8464:(4): 1151–62. 8444: 8411:Cancer Letters 8394: 8373:(5): 1268–74. 8353: 8312: 8269: 8220: 8179: 8130: 8105: 8079: 8067: 8016: 7957: 7936:(5): 1160–71. 7916: 7889:(5): 3851–57. 7872: 7851:(8): 2265–72. 7831: 7804:(7): 1017–26. 7787: 7736: 7695: 7666:(6): 797–802. 7646: 7603: 7554: 7503: 7447: 7426:(2): 196–227. 7406: 7357: 7322:Carcinogenesis 7308: 7269:(7): 3122–27. 7249: 7198: 7146: 7105: 7076:(7): 2225–38. 7056: 7007: 6961: 6910: 6853: 6826:Carcinogenesis 6809: 6758: 6707: 6653: 6602: 6549: 6514: 6463: 6414: 6363: 6352: 6330: 6306: 6263: 6214: 6195:(3): 295–307. 6178: 6127: 6076: 6047:(12): 952–65. 6027: 5984: 5957: 5942: 5915:(1–2): 22–35. 5898: 5841: 5792: 5757: 5722: 5678: 5657:(3): 599–610. 5637: 5606: 5599: 5577: 5570: 5552: 5501: 5458: 5406: 5362: 5313: 5284:(5): 887–900. 5264: 5218: 5174: 5122: 5093:(24): 3791–9. 5068: 5039:(14): 2233–7. 5019: 4970: 4956: 4921: 4895: 4866:(12): 2330–8. 4846: 4817:(31): 8070–9. 4797: 4748: 4720: 4669: 4618: 4569: 4530:(19): 7720–5. 4507: 4478:(2): 299–311. 4458: 4367: 4318: 4277: 4228: 4199:(5): 2164–73. 4179: 4122: 4078: 4035: 4012: 4005: 3987: 3972: 3939: 3932: 3914: 3907: 3884: 3833: 3805: 3776:(5): 1143–53. 3756: 3737:(6): 2203–37. 3721: 3684:10.1.1.318.738 3677:(3): 199–208. 3649: 3606: 3571: 3530: 3481: 3440: 3433: 3415: 3380: 3349: 3321: 3292:(11): 851–60. 3276: 3261: 3240: 3211: 3210: 3208: 3205: 3203: 3202: 3190: 3185: 3180: 3175: 3170: 3168:Life extension 3165: 3160: 3155: 3150: 3145: 3140: 3135: 3130: 3125: 3120: 3115: 3109: 3108: 3107: 3104:Biology portal 3091: 3088: 3079: 3076: 3054: 3051: 3035:photosynthetic 2998:bacteriophages 2981: 2978: 2970: 2967: 2945: 2942: 2891: 2887: 2883: 2879: 2875: 2871: 2847: 2843: 2835: 2831: 2776:Initiation of 2751: 2748: 2738: 2735: 2706: 2703: 2691:epigenetically 2604:carcinogenesis 2531: 2528: 2489:cell divisions 2452: 2449: 2440: 2439: 2432: 2430: 2428: 2426: 2419: 2417: 2410: 2406: 2405: 2403: 2396: 2394: 2387: 2380: 2378: 2371: 2367: 2366: 2364: 2362: 2355: 2353: 2351: 2344: 2342: 2336: 2335: 2328: 2321: 2314: 2312: 2310: 2308: 2306: 2302: 2301: 2299: 2292: 2285: 2283: 2281: 2279: 2277: 2273: 2272: 2270: 2263: 2256: 2254: 2252: 2250: 2243: 2239: 2238: 2236: 2234: 2232: 2225: 2223: 2221: 2214: 2210: 2209: 2207: 2205: 2203: 2196: 2194: 2192: 2185: 2179: 2178: 2176: 2174: 2172: 2165: 2163: 2161: 2154: 2148: 2147: 2145: 2138: 2136: 2134: 2127: 2125: 2118: 2114: 2113: 2111: 2109: 2107: 2105: 2103: 2096: 2089: 2085: 2084: 2082: 2080: 2078: 2076: 2069: 2062: 2055: 2051: 2050: 2048: 2046: 2044: 2042: 2035: 2028: 2021: 2017: 2016: 2013: 2010: 2007: 2004: 2001: 1998: 1995: 1955: 1952: 1891: 1888: 1876:Fanconi anemia 1861: 1860: 1854: 1840: 1827: 1826: 1820: 1814: 1803: 1800: 1795:Main article: 1792: 1789: 1783:theory of the 1744:metabolic rate 1722: 1719: 1658: 1655: 1650:Main article: 1647: 1644: 1619:may be in the 1616:shock response 1595: 1592: 1571:ATP hydrolysis 1546:that binds to 1506: 1503: 1461:protein kinase 1364: 1361: 1228:complexes and 1209: 1206: 1153: 1150: 1099:T^T photodimer 1091:UV irradiation 1066:thymine dimers 1057: 1054: 1042:Topoisomerases 992: 991: 971: 944: 865: 862: 861: 860: 846: 828: 784: 781: 768:stoichiometric 721: 718: 694:Main article: 691: 688: 665: 662: 642:Hayflick limit 625: 622: 553: 550: 546:ring puckering 542: 541: 526:vinyl chloride 519: 489: 474: 458: 428: 427: 424: 421: 411: 405: 389: 370: 357: 354: 341: 340: 339: 338: 333: 319: 310: 304: 294: 277: 276: 275: 271:also includes 251: 248: 184: 181: 137: 136: 126: 116: 26: 9: 6: 4: 3: 2: 10741: 10730: 10727: 10725: 10722: 10720: 10717: 10715: 10712: 10710: 10707: 10706: 10704: 10694: 10689: 10684: 10683: 10680: 10667: 10659: 10658: 10655: 10649: 10646: 10644: 10641: 10639: 10636: 10634: 10631: 10629: 10626: 10622: 10619: 10617: 10614: 10612: 10609: 10607: 10604: 10602: 10599: 10597: 10594: 10592: 10589: 10587: 10584: 10583: 10582: 10578: 10577:FANC proteins 10575: 10574: 10571: 10568: 10566: 10562: 10559: 10558: 10555: 10552: 10550: 10547: 10545: 10542: 10540: 10537: 10535: 10532: 10530: 10527: 10526: 10524: 10520: 10514: 10511: 10509: 10506: 10505: 10503: 10499: 10491: 10488: 10486: 10483: 10482: 10481: 10478: 10476: 10473: 10471: 10468: 10464: 10461: 10460: 10459: 10456: 10454: 10451: 10447: 10444: 10442: 10439: 10438: 10437: 10434: 10433: 10431: 10427: 10421: 10418: 10416: 10413: 10411: 10408: 10406: 10403: 10399: 10398:RecQ helicase 10396: 10395: 10394: 10391: 10389: 10386: 10384: 10381: 10380: 10378: 10376: 10372: 10364: 10361: 10359: 10356: 10355: 10354: 10351: 10347: 10344: 10342: 10339: 10337: 10334: 10332: 10329: 10327: 10324: 10322: 10319: 10317: 10314: 10312: 10309: 10307: 10304: 10302: 10299: 10297: 10294: 10292: 10289: 10288: 10287: 10283: 10280: 10276: 10273: 10271: 10268: 10266: 10263: 10262: 10261: 10257: 10254: 10253: 10251: 10249: 10245: 10241: 10234: 10229: 10227: 10222: 10220: 10215: 10214: 10211: 10203: 10199: 10194: 10189: 10184: 10179: 10175: 10171: 10167: 10163: 10159: 10154: 10150: 10146: 10141: 10136: 10132: 10128: 10124: 10120: 10116: 10111: 10109: 10106: 10104: 10101: 10099: 10095: 10092: 10089: 10087: 10084: 10079: 10074: 10070: 10066: 10062: 10057: 10055: 10052: 10050: 10047: 10045: 10042: 10039: 10034: 10030: 10029: 10025: 10021: 10006: 9964: 9961: 9959: 9956: 9954: 9951: 9950: 9945: 9940: 9924: 9919: 9911: 9907: 9902: 9897: 9893: 9889: 9885: 9878: 9870: 9866: 9862: 9858: 9855:(2): 720–52. 9854: 9850: 9843: 9835: 9831: 9826: 9821: 9817: 9813: 9809: 9802: 9794: 9790: 9785: 9780: 9776: 9772: 9768: 9764: 9760: 9753: 9745: 9741: 9736: 9731: 9726: 9721: 9717: 9713: 9709: 9702: 9694: 9690: 9685: 9680: 9676: 9672: 9668: 9664: 9660: 9656: 9652: 9645: 9637: 9633: 9628: 9623: 9619: 9615: 9612:(1): 126–40. 9611: 9607: 9606:Hum Mol Genet 9603: 9596: 9588: 9584: 9579: 9574: 9569: 9564: 9560: 9556: 9552: 9545: 9543: 9534: 9530: 9525: 9520: 9515: 9510: 9506: 9502: 9498: 9494: 9490: 9483: 9475: 9471: 9466: 9461: 9456: 9451: 9447: 9443: 9439: 9432: 9430: 9421: 9417: 9412: 9407: 9403: 9399: 9396:(3): 244–54. 9395: 9391: 9387: 9380: 9372: 9368: 9363: 9358: 9354: 9350: 9346: 9342: 9338: 9331: 9323: 9319: 9314: 9309: 9305: 9301: 9297: 9293: 9289: 9282: 9274: 9270: 9266: 9262: 9258: 9254: 9247: 9239: 9235: 9230: 9225: 9220: 9215: 9211: 9207: 9203: 9199: 9195: 9188: 9180: 9176: 9171: 9166: 9161: 9156: 9152: 9148: 9147:Int J Mol Sci 9144: 9137: 9129: 9125: 9120: 9115: 9111: 9107: 9103: 9099: 9095: 9088: 9080: 9076: 9072: 9068: 9064: 9060: 9053: 9051: 9049: 9040: 9036: 9031: 9026: 9022: 9018: 9014: 9010: 9009:J Am Chem Soc 9006: 8999: 8991: 8987: 8982: 8977: 8973: 8969: 8965: 8961: 8957: 8950: 8948: 8939: 8935: 8930: 8925: 8921: 8917: 8913: 8909: 8905: 8898: 8890: 8886: 8881: 8876: 8872: 8868: 8864: 8860: 8856: 8849: 8841: 8837: 8832: 8827: 8822: 8817: 8813: 8809: 8805: 8798: 8790: 8786: 8781: 8776: 8772: 8768: 8764: 8760: 8756: 8749: 8741: 8737: 8732: 8727: 8723: 8719: 8715: 8711: 8707: 8700: 8698: 8689: 8685: 8680: 8675: 8671: 8667: 8663: 8659: 8655: 8651: 8647: 8640: 8632: 8628: 8623: 8618: 8613: 8608: 8604: 8600: 8596: 8589: 8581: 8577: 8572: 8567: 8562: 8557: 8553: 8549: 8545: 8538: 8530: 8526: 8521: 8516: 8512: 8508: 8504: 8497: 8489: 8485: 8480: 8475: 8471: 8467: 8463: 8459: 8455: 8448: 8440: 8436: 8432: 8428: 8424: 8420: 8417:(1): 111–20. 8416: 8412: 8405: 8398: 8390: 8386: 8381: 8376: 8372: 8368: 8364: 8357: 8349: 8345: 8340: 8335: 8331: 8327: 8323: 8316: 8308: 8304: 8300: 8296: 8292: 8288: 8285:(2): 445–51. 8284: 8280: 8273: 8265: 8261: 8256: 8251: 8247: 8243: 8239: 8235: 8231: 8224: 8216: 8212: 8207: 8202: 8198: 8194: 8190: 8183: 8175: 8171: 8166: 8161: 8157: 8153: 8150:(2): 230–42. 8149: 8145: 8141: 8134: 8126: 8122: 8117: 8112: 8108: 8102: 8098: 8094: 8090: 8083: 8076: 8071: 8063: 8059: 8054: 8049: 8044: 8039: 8035: 8031: 8027: 8020: 8012: 8008: 8003: 7998: 7993: 7988: 7984: 7980: 7976: 7972: 7968: 7961: 7953: 7949: 7944: 7939: 7935: 7931: 7927: 7920: 7912: 7908: 7904: 7900: 7896: 7892: 7888: 7884: 7876: 7868: 7864: 7859: 7854: 7850: 7846: 7842: 7835: 7827: 7823: 7819: 7815: 7811: 7807: 7803: 7799: 7791: 7783: 7779: 7774: 7769: 7764: 7759: 7755: 7751: 7747: 7740: 7732: 7728: 7723: 7718: 7714: 7710: 7706: 7699: 7691: 7687: 7682: 7677: 7673: 7669: 7665: 7661: 7657: 7650: 7642: 7638: 7634: 7630: 7626: 7622: 7618: 7614: 7607: 7599: 7595: 7590: 7585: 7581: 7577: 7574:(4): 475–84. 7573: 7569: 7565: 7558: 7550: 7546: 7541: 7536: 7531: 7526: 7522: 7518: 7517:PLOS Genetics 7514: 7507: 7499: 7495: 7490: 7485: 7480: 7475: 7471: 7467: 7466:PLOS Genetics 7463: 7456: 7454: 7452: 7443: 7439: 7434: 7429: 7425: 7421: 7417: 7410: 7402: 7398: 7393: 7388: 7384: 7380: 7377:(3): 255–60. 7376: 7372: 7368: 7361: 7353: 7349: 7344: 7339: 7335: 7331: 7327: 7323: 7319: 7312: 7304: 7300: 7295: 7290: 7285: 7280: 7276: 7272: 7268: 7264: 7260: 7253: 7245: 7241: 7236: 7231: 7226: 7221: 7217: 7213: 7209: 7202: 7196: 7191: 7187: 7182: 7177: 7173: 7169: 7165: 7161: 7157: 7150: 7142: 7138: 7133: 7128: 7125:(4): 247–53. 7124: 7120: 7116: 7109: 7101: 7097: 7092: 7087: 7083: 7079: 7075: 7071: 7067: 7060: 7052: 7048: 7043: 7038: 7034: 7030: 7027:(4): 303–11. 7026: 7022: 7018: 7011: 7003: 6999: 6995: 6991: 6987: 6983: 6980:(2): 107–16. 6979: 6975: 6971: 6965: 6957: 6953: 6948: 6943: 6938: 6933: 6929: 6925: 6921: 6914: 6906: 6902: 6897: 6892: 6888: 6884: 6880: 6876: 6873:(2): 111–30. 6872: 6868: 6864: 6857: 6849: 6845: 6840: 6835: 6832:(3): 453–60. 6831: 6827: 6820: 6813: 6805: 6801: 6797: 6793: 6789: 6785: 6781: 6777: 6773: 6769: 6762: 6754: 6750: 6746: 6742: 6738: 6734: 6730: 6726: 6723:(5): 276–89. 6722: 6718: 6711: 6703: 6699: 6695: 6691: 6687: 6683: 6679: 6675: 6671: 6667: 6660: 6658: 6649: 6645: 6641: 6637: 6633: 6629: 6625: 6621: 6617: 6613: 6606: 6598: 6594: 6590: 6586: 6582: 6578: 6574: 6570: 6563: 6556: 6554: 6545: 6541: 6537: 6533: 6529: 6525: 6518: 6510: 6506: 6502: 6498: 6494: 6490: 6486: 6482: 6478: 6474: 6467: 6459: 6455: 6450: 6445: 6441: 6437: 6433: 6429: 6425: 6418: 6410: 6406: 6401: 6396: 6391: 6386: 6382: 6378: 6374: 6367: 6360: 6355: 6349: 6345: 6341: 6334: 6327: 6323: 6322: 6317: 6310: 6302: 6298: 6294: 6290: 6286: 6282: 6278: 6274: 6267: 6259: 6255: 6251: 6247: 6242: 6237: 6234:(3): 595–97. 6233: 6229: 6228:FASEB Journal 6225: 6218: 6210: 6206: 6202: 6198: 6194: 6190: 6182: 6174: 6170: 6166: 6162: 6158: 6154: 6150: 6146: 6142: 6138: 6131: 6123: 6119: 6115: 6111: 6107: 6103: 6099: 6095: 6091: 6087: 6080: 6072: 6068: 6063: 6058: 6054: 6050: 6046: 6042: 6038: 6031: 6023: 6019: 6015: 6011: 6007: 6003: 6000:(9): 960–66. 5999: 5995: 5988: 5980: 5976: 5973:(3): 134–35. 5972: 5968: 5961: 5951: 5949: 5947: 5938: 5934: 5930: 5926: 5922: 5918: 5914: 5910: 5902: 5894: 5890: 5886: 5882: 5877: 5872: 5868: 5864: 5860: 5856: 5852: 5845: 5837: 5833: 5828: 5823: 5819: 5815: 5812:(5): 503–09. 5811: 5807: 5803: 5796: 5788: 5784: 5780: 5776: 5772: 5768: 5761: 5753: 5749: 5745: 5741: 5738:(2): 406–19. 5737: 5733: 5726: 5718: 5714: 5709: 5704: 5701:(6): 637–56. 5700: 5696: 5692: 5685: 5683: 5674: 5670: 5665: 5660: 5656: 5652: 5648: 5641: 5633: 5629: 5626:(8): 639–49. 5625: 5621: 5617: 5610: 5602: 5596: 5591: 5590: 5581: 5573: 5567: 5563: 5556: 5548: 5544: 5540: 5536: 5532: 5528: 5524: 5520: 5516: 5512: 5505: 5497: 5493: 5489: 5485: 5481: 5477: 5473: 5469: 5462: 5454: 5450: 5445: 5440: 5436: 5432: 5429:(2): 235–49. 5428: 5424: 5420: 5413: 5411: 5402: 5398: 5393: 5388: 5384: 5380: 5376: 5369: 5367: 5358: 5354: 5349: 5344: 5340: 5336: 5332: 5328: 5324: 5317: 5309: 5305: 5301: 5297: 5292: 5287: 5283: 5279: 5275: 5268: 5260: 5256: 5251: 5246: 5242: 5238: 5234: 5227: 5225: 5223: 5214: 5210: 5205: 5200: 5196: 5192: 5188: 5181: 5179: 5170: 5166: 5161: 5156: 5152: 5148: 5144: 5140: 5136: 5129: 5127: 5118: 5114: 5109: 5104: 5100: 5096: 5092: 5088: 5084: 5077: 5075: 5073: 5064: 5060: 5055: 5050: 5046: 5042: 5038: 5034: 5030: 5023: 5015: 5011: 5006: 5001: 4997: 4993: 4990:(7): 533–47. 4989: 4985: 4981: 4974: 4965: 4963: 4961: 4952: 4948: 4944: 4940: 4936: 4932: 4925: 4909: 4905: 4899: 4891: 4887: 4882: 4877: 4873: 4869: 4865: 4861: 4857: 4850: 4842: 4838: 4833: 4828: 4824: 4820: 4816: 4812: 4808: 4801: 4793: 4789: 4784: 4779: 4775: 4771: 4768:(1): 134–54. 4767: 4763: 4759: 4752: 4745: 4741: 4735: 4731: 4724: 4716: 4712: 4708: 4704: 4700: 4696: 4692: 4688: 4684: 4680: 4673: 4665: 4661: 4656: 4651: 4646: 4641: 4637: 4633: 4629: 4622: 4614: 4610: 4605: 4600: 4596: 4592: 4588: 4584: 4580: 4573: 4565: 4561: 4556: 4551: 4546: 4541: 4537: 4533: 4529: 4525: 4521: 4514: 4512: 4503: 4499: 4495: 4491: 4486: 4481: 4477: 4473: 4469: 4462: 4450: 4442: 4435: 4431: 4427: 4423: 4419: 4412: 4408: 4403: 4398: 4394: 4390: 4386: 4382: 4378: 4371: 4363: 4359: 4354: 4349: 4345: 4341: 4338:(4): 849–60. 4337: 4333: 4329: 4322: 4314: 4310: 4305: 4300: 4296: 4292: 4288: 4281: 4273: 4269: 4264: 4259: 4255: 4251: 4247: 4243: 4239: 4232: 4224: 4220: 4215: 4210: 4206: 4202: 4198: 4194: 4190: 4183: 4175: 4171: 4167: 4163: 4158: 4157:10.1038/41365 4153: 4149: 4145: 4141: 4137: 4133: 4126: 4118: 4114: 4109: 4104: 4100: 4096: 4092: 4085: 4083: 4074: 4070: 4066: 4062: 4058: 4054: 4051:(7): 561–74. 4050: 4046: 4039: 4031: 4027: 4024:(1): 254–60. 4023: 4016: 4008: 4002: 3998: 3991: 3983: 3979: 3975: 3969: 3965: 3961: 3957: 3950: 3948: 3946: 3944: 3935: 3929: 3925: 3918: 3910: 3904: 3900: 3893: 3891: 3889: 3880: 3876: 3872: 3868: 3864: 3860: 3856: 3852: 3849:(2): 241–55. 3848: 3844: 3837: 3829: 3825: 3821: 3814: 3812: 3810: 3801: 3797: 3792: 3787: 3783: 3779: 3775: 3771: 3767: 3760: 3752: 3748: 3744: 3740: 3736: 3732: 3725: 3706: 3702: 3698: 3694: 3690: 3685: 3680: 3676: 3672: 3665: 3658: 3656: 3654: 3645: 3641: 3637: 3633: 3629: 3625: 3622:(9): 729–40. 3621: 3617: 3610: 3602: 3598: 3594: 3590: 3586: 3582: 3575: 3567: 3563: 3558: 3553: 3550:(6): 2881–4. 3549: 3545: 3541: 3534: 3526: 3522: 3517: 3512: 3508: 3504: 3500: 3496: 3492: 3485: 3476: 3471: 3467: 3463: 3459: 3455: 3451: 3444: 3436: 3430: 3426: 3419: 3411: 3407: 3403: 3399: 3395: 3391: 3384: 3369: 3368: 3360: 3353: 3338: 3337: 3332: 3325: 3317: 3313: 3309: 3305: 3300: 3295: 3291: 3287: 3280: 3272: 3268: 3264: 3258: 3254: 3247: 3245: 3229:. 5 July 2017 3228: 3227: 3222: 3216: 3212: 3201: 3200: 3195: 3191: 3189: 3186: 3184: 3181: 3179: 3176: 3174: 3171: 3169: 3166: 3164: 3161: 3159: 3156: 3154: 3151: 3149: 3146: 3144: 3141: 3139: 3136: 3134: 3131: 3129: 3126: 3124: 3121: 3119: 3116: 3114: 3111: 3110: 3105: 3099: 3094: 3087: 3085: 3075: 3072: 3068: 3064: 3060: 3050: 3048: 3044: 3040: 3039:free radicals 3036: 3032: 3027: 3026:Nucleic acids 3023: 3019: 3018:fossil record 3014: 3011: 3007: 3004:which infect 3003: 2999: 2995: 2991: 2987: 2977: 2975: 2966: 2962: 2959: 2955: 2951: 2941: 2938: 2934: 2933:messenger RNA 2929: 2925: 2921: 2917: 2913: 2909: 2905: 2901: 2900:HEK 293 cells 2896: 2868: 2866: 2862: 2859: 2855: 2854: 2841: 2828: 2826: 2822: 2817: 2815: 2807: 2803: 2799: 2795: 2791: 2787: 2783: 2779: 2774: 2770: 2768: 2764: 2761: 2757: 2747: 2745: 2734: 2732: 2728: 2724: 2720: 2717: 2713: 2702: 2700: 2696: 2692: 2688: 2684: 2679: 2675: 2670: 2668: 2664: 2660: 2656: 2652: 2648: 2644: 2640: 2636: 2632: 2628: 2624: 2620: 2619: 2614: 2613: 2607: 2605: 2601: 2597: 2591: 2587: 2583: 2581: 2577: 2572: 2570: 2566: 2562: 2558: 2553: 2551: 2547: 2536: 2527: 2525: 2521: 2516: 2512: 2510: 2506: 2500: 2498: 2492: 2490: 2486: 2482: 2478: 2474: 2470: 2466: 2461: 2459: 2431: 2429: 2427: 2418: 2408: 2407: 2404: 2395: 2379: 2369: 2368: 2365: 2363: 2354: 2352: 2343: 2341: 2338: 2337: 2313: 2311: 2309: 2307: 2304: 2303: 2300: 2284: 2282: 2280: 2278: 2275: 2274: 2271: 2255: 2253: 2251: 2241: 2240: 2237: 2235: 2233: 2224: 2222: 2212: 2211: 2208: 2206: 2204: 2195: 2193: 2184: 2181: 2180: 2177: 2175: 2173: 2164: 2162: 2153: 2150: 2149: 2146: 2137: 2135: 2126: 2116: 2115: 2112: 2110: 2108: 2106: 2104: 2087: 2086: 2083: 2081: 2079: 2077: 2053: 2052: 2049: 2047: 2045: 2043: 2019: 2018: 2014: 2011: 2008: 2005: 2002: 1999: 1996: 1994: 1993: 1990: 1987: 1981: 1979: 1975: 1971: 1965: 1962: 1951: 1947: 1944: 1940: 1936: 1932: 1927: 1924: 1920: 1915: 1913: 1912: 1907: 1906: 1901: 1897: 1887: 1885: 1881: 1880:breast cancer 1878:, hereditary 1877: 1872: 1870: 1866: 1858: 1855: 1852: 1848: 1844: 1841: 1838: 1835: 1834: 1833: 1830: 1824: 1821: 1818: 1815: 1812: 1809: 1808: 1807: 1798: 1788: 1786: 1782: 1777: 1772: 1770: 1769: 1764: 1759: 1757: 1753: 1749: 1745: 1741: 1737: 1727: 1718: 1716: 1715:radioactivity 1712: 1711: 1706: 1700: 1698: 1693: 1689: 1685: 1681: 1676: 1673: 1663: 1653: 1643: 1641: 1637: 1633: 1628: 1626: 1622: 1621:heterogeneity 1617: 1613: 1612: 1608: 1604: 1600: 1591: 1588: 1584: 1579: 1576: 1572: 1568: 1564: 1560: 1555: 1554: 1549: 1545: 1542: 1538: 1534: 1530: 1526: 1522: 1521: 1516: 1512: 1502: 1500: 1496: 1492: 1489: 1485: 1481: 1476: 1474: 1470: 1466: 1462: 1458: 1453: 1451: 1447: 1443: 1439: 1435: 1431: 1429: 1425: 1421: 1417: 1413: 1412:phosphorylate 1409: 1405: 1401: 1397: 1393: 1389: 1385: 1381: 1377: 1373: 1370: 1360: 1358: 1354: 1350: 1346: 1342: 1339: 1335: 1330: 1328: 1324: 1320: 1316: 1312: 1308: 1304: 1300: 1296: 1292: 1290: 1286: 1282: 1277: 1273: 1268: 1266: 1261: 1257: 1254: 1250: 1246: 1242: 1238: 1233: 1231: 1227: 1223: 1219: 1215: 1208:Initial steps 1205: 1203: 1202:cell division 1199: 1195: 1191: 1187: 1183: 1179: 1175: 1174:carbohydrates 1171: 1167: 1163: 1159: 1149: 1147: 1142: 1139: 1135: 1131: 1126: 1122: 1117: 1112: 1108: 1104: 1100: 1096: 1092: 1088: 1084: 1080: 1075: 1071: 1067: 1063: 1053: 1049: 1047: 1043: 1039: 1037: 1033: 1029: 1025: 1021: 1017: 1013: 1009: 1008: 1004: 999: 997: 989: 985: 981: 977: 972: 969: 965: 961: 957: 953: 949: 948:end resection 945: 942: 941:immune system 939: 935: 931: 927: 923: 919: 915: 911: 910:DNA Ligase IV 907: 906: 902: 897: 893: 891: 887: 883: 879: 870: 858: 854: 850: 847: 844: 840: 839:endonucleases 836: 832: 829: 825: 822: 818: 814: 810: 807: 806: 805: 803: 794: 789: 780: 777: 773: 769: 765: 760: 756: 752: 748: 744: 740: 739:blue/UV light 736: 732: 728: 717: 713: 711: 707: 703: 697: 687: 683: 679: 675: 672: 661: 659: 655: 651: 647: 643: 639: 638:noncoding DNA 635: 631: 621: 619: 615: 611: 607: 603: 599: 598:free radicals 595: 591: 587: 583: 582:cell division 579: 575: 571: 567: 563: 559: 549: 547: 539: 535: 531: 527: 523: 520: 517: 513: 509: 505: 501: 497: 493: 490: 486: 485: 480: 479: 475: 472: 468: 467:free radicals 464: 463: 459: 456: 452: 451: 446: 442: 438: 437: 433: 432: 431: 425: 422: 419: 415: 412: 409: 406: 403: 399: 395: 394: 390: 388: 384: 380: 376: 375: 371: 368: 367: 363: 362: 361: 353: 351: 347: 346:back mutation 337: 334: 332: 328: 325:, especially 324: 320: 318: 315: 311: 308: 305: 303: 299: 295: 292: 288: 284: 281: 280: 278: 274: 270: 269: 268: 264: 260: 257: 256: 255: 247: 245: 241: 237: 233: 229: 225: 220: 215: 213: 209: 205: 200: 194: 190: 180: 178: 174: 170: 169:Tomas Lindahl 166: 144: 142: 135: 131: 127: 125: 121: 117: 115: 111: 110: 109: 105: 103: 99: 95: 91: 87: 83: 79: 75: 71: 67: 63: 59: 55: 51: 43: 39: 35: 30: 19: 10580: 10561:DNA helicase 10544:8-Oxoguanine 10513:SOS response 10393:RecF pathway 10346:Excinuclease 10239: 10165: 10161: 10122: 10118: 10068: 10064: 9953:Online books 9943: 9918: 9894:(1): 38–46. 9891: 9887: 9877: 9852: 9848: 9842: 9815: 9811: 9801: 9766: 9762: 9752: 9715: 9712:BMC Genomics 9711: 9701: 9658: 9654: 9644: 9609: 9605: 9595: 9558: 9554: 9496: 9492: 9482: 9445: 9441: 9393: 9389: 9379: 9344: 9340: 9330: 9298:(1): 23–38. 9295: 9291: 9281: 9256: 9252: 9246: 9201: 9197: 9187: 9153:(21): 8360. 9150: 9146: 9136: 9101: 9097: 9087: 9062: 9058: 9012: 9008: 8998: 8963: 8959: 8911: 8907: 8897: 8865:(1): 71–75. 8862: 8858: 8848: 8811: 8807: 8797: 8762: 8758: 8748: 8713: 8710:Cell Reports 8709: 8653: 8649: 8639: 8602: 8598: 8588: 8551: 8547: 8537: 8510: 8506: 8496: 8461: 8457: 8447: 8414: 8410: 8397: 8370: 8366: 8356: 8329: 8325: 8315: 8282: 8278: 8272: 8237: 8233: 8223: 8196: 8192: 8182: 8147: 8143: 8133: 8088: 8082: 8070: 8033: 8029: 8019: 7974: 7970: 7960: 7933: 7929: 7919: 7886: 7882: 7875: 7848: 7844: 7834: 7801: 7797: 7790: 7753: 7749: 7739: 7712: 7708: 7698: 7663: 7659: 7649: 7616: 7612: 7606: 7571: 7567: 7557: 7520: 7516: 7506: 7469: 7465: 7423: 7419: 7409: 7374: 7371:EMBO Reports 7370: 7360: 7325: 7321: 7311: 7266: 7262: 7252: 7218:(3): 43–49. 7215: 7211: 7201: 7166:(1): 51–58. 7163: 7159: 7149: 7122: 7118: 7108: 7073: 7069: 7059: 7024: 7020: 7010: 6977: 6973: 6964: 6927: 6923: 6913: 6870: 6866: 6856: 6829: 6825: 6812: 6771: 6767: 6761: 6737:10261/123721 6720: 6716: 6710: 6669: 6665: 6615: 6611: 6605: 6575:(1): 35–42. 6572: 6568: 6527: 6523: 6517: 6476: 6472: 6466: 6431: 6427: 6417: 6380: 6376: 6366: 6357: 6343: 6333: 6325: 6319: 6309: 6276: 6272: 6266: 6231: 6227: 6217: 6192: 6188: 6181: 6140: 6136: 6130: 6089: 6085: 6079: 6044: 6040: 6030: 5997: 5993: 5987: 5970: 5966: 5960: 5912: 5908: 5901: 5858: 5854: 5844: 5809: 5806:EMBO Reports 5805: 5795: 5770: 5766: 5760: 5735: 5731: 5725: 5698: 5694: 5654: 5650: 5640: 5623: 5619: 5609: 5588: 5580: 5561: 5555: 5514: 5510: 5504: 5474:(1): 37–45. 5471: 5467: 5461: 5426: 5422: 5382: 5378: 5330: 5326: 5316: 5281: 5277: 5267: 5240: 5236: 5194: 5190: 5142: 5139:Cell Reports 5138: 5090: 5086: 5036: 5032: 5022: 4987: 4983: 4973: 4937:(2): 59–70. 4934: 4930: 4924: 4912:. Retrieved 4908:the original 4898: 4863: 4860:Biochemistry 4859: 4849: 4814: 4811:Biochemistry 4810: 4800: 4765: 4761: 4751: 4729: 4723: 4682: 4678: 4672: 4635: 4631: 4621: 4589:(3): e1697. 4586: 4582: 4572: 4527: 4523: 4475: 4471: 4461: 4447:{{ 4439:{{ 4384: 4380: 4370: 4335: 4331: 4321: 4294: 4290: 4280: 4245: 4241: 4231: 4196: 4192: 4182: 4139: 4135: 4125: 4098: 4094: 4048: 4044: 4038: 4021: 4015: 3996: 3990: 3955: 3923: 3917: 3898: 3846: 3842: 3836: 3819: 3773: 3769: 3759: 3734: 3730: 3724: 3714:29 September 3712:. Retrieved 3705:the original 3674: 3670: 3619: 3615: 3609: 3587:(2): 69–78. 3584: 3580: 3574: 3547: 3543: 3533: 3498: 3494: 3484: 3460:(2): 56–61. 3457: 3453: 3443: 3424: 3418: 3393: 3389: 3383: 3371:. Retrieved 3365: 3352: 3340:. Retrieved 3334: 3324: 3289: 3285: 3279: 3252: 3231:. Retrieved 3224: 3215: 3197: 3193: 3153:Gene therapy 3081: 3056: 3015: 2983: 2972: 2963: 2947: 2910:(K2CrO4)). 2897: 2869: 2864: 2857: 2852: 2829: 2823:it recruits 2818: 2811: 2753: 2740: 2708: 2677: 2671: 2666: 2662: 2654: 2650: 2646: 2642: 2638: 2634: 2616: 2610: 2608: 2599: 2592: 2588: 2584: 2573: 2554: 2542: 2517: 2513: 2501: 2493: 2485:DNA sequence 2462: 2454: 1982: 1966: 1957: 1948: 1933:) inhibitor 1928: 1923:radiotherapy 1919:chemotherapy 1916: 1909: 1903: 1893: 1884:colon cancer 1873: 1862: 1849:(especially 1847:malignancies 1831: 1828: 1805: 1775: 1773: 1766: 1760: 1732: 1708: 1701: 1677: 1668: 1629: 1609: 1597: 1582: 1580: 1567:DNA helicase 1551: 1518: 1511:SOS response 1508: 1477: 1459:(PI3K)-like 1454: 1440:that blocks 1433: 1432: 1366: 1332:After rapid 1331: 1293: 1269: 1234: 1211: 1166:biomolecules 1155: 1124: 1120: 1079:processivity 1059: 1050: 1046:supercoiling 1040: 1030:by means of 1005: 1003:extremophile 1000: 995: 993: 888:(MMEJ), and 875: 856: 853:proofreading 843:Uvr proteins 798: 770:rather than 723: 714: 699: 684: 680: 676: 667: 627: 566:mitochondria 555: 543: 521: 496:depurination 491: 482: 476: 460: 448: 434: 429: 413: 402:depurination 391: 372: 364: 359: 342: 253: 216: 196: 173:Paul Modrich 162: 138: 106: 49: 48: 38: 29: 9561:(7): e110. 9253:Cell Signal 9104:: 207–219. 9059:Cell Signal 8908:Toxicol Sci 8831:10230/35343 7523:(7): e110. 7119:Mutagenesis 4730:Radiat Res. 4420:, see 3396:: 577–628. 3367:Nobel Prize 3178:REPAIRtoire 3022:Precambrian 2990:prokaryotes 2988:among both 2906:(KBrO3) or 2788:), forming 1763:gene dosage 1640:polymerases 1587:palindromic 1559:Spirochetes 1535:. The LexA 1525:prokaryotic 1501:complexes. 1473:chromosomes 1372:checkpoints 1341:checkpoints 1116:polymerases 1034:-dependent 813:glycosylase 753:, and most 578:chromosomes 508:hot springs 484:cosmic rays 398:deamination 379:methylation 321:human-made 283:ultraviolet 240:supercoiled 177:Aziz Sancar 100:as per the 10729:Senescence 10709:DNA repair 10703:Categories 10501:Regulation 10480:Photolyase 10240:DNA repair 10091:DNA Repair 10038:DNA repair 10020:Audio help 10011:2005-06-17 9944:DNA repair 9763:Oncotarget 9718:(1): 856. 9555:PLOS Genet 9448:(1): 225. 8599:BMC Cancer 8554:: 946268. 6530:: 129–43. 6377:BMC Cancer 6189:DNA Repair 5773:: 357–77. 5033:Cell Cycle 3924:i Genetics 3495:Cell Cycle 3233:7 November 3207:References 3194:DNA Repair 3183:Senescence 3123:Cell cycle 3078:Technology 3033:") due to 2994:eukaryotes 2861:CpG island 2840:TET enzyme 2760:methylated 2678:inaccurate 1986:cell cycle 1781:pleiotropy 1776:C. elegans 1756:DNA damage 1599:Eukaryotic 1442:cell cycle 1369:cell cycle 1338:cell cycle 1224:dependent 1198:cell cycle 1093:, whereas 1020:homologous 938:vertebrate 922:eukaryotes 914:DNA ligase 743:wavelength 735:photolyase 690:Mechanisms 650:cell cycle 646:quiescence 604:(ATP) via 596:(ROS), or 590:organelles 574:cell cycle 558:eukaryotic 462:UV-A light 436:UV-B light 393:hydrolysis 374:alkylation 307:hydrolysis 302:gamma rays 259:endogenous 183:DNA damage 114:senescence 78:transcribe 50:DNA repair 10321:XPG/ERCC5 10306:XPD/ERCC2 9661:: 33222. 6970:Baylin SB 6930:(4): 14. 6434:: 65–83. 4914:14 August 3828:936762772 3679:CiteSeerX 3373:7 October 3342:7 October 3294:CiteSeerX 3118:Aging DNA 3071:evolution 3063:germ line 3059:mutations 2986:conserved 2980:Evolution 2958:CpG sites 2786:CpG sites 2481:microRNAs 1865:progerias 1851:leukemias 1697:longevity 1625:mammalian 1544:repressor 1537:homodimer 1484:apoptosis 1446:metaphase 1329:damages. 1315:PARylates 1309:and with 1253:polymeric 1218:remodeled 1214:chromatin 1190:apoptosis 1028:crossover 1016:annealing 980:chromatid 908:In NHEJ, 772:catalytic 706:chromatid 634:telomeres 618:cytoplasm 570:chromatin 498:(loss of 366:oxidation 289:(200–400 287:radiation 199:metabolic 163:The 2015 141:life span 134:cancerous 120:apoptosis 94:apoptosis 86:mutations 70:radiation 66:metabolic 10724:Mutation 10666:Category 10316:XPF/DDB1 10311:XPE/DDB1 10202:26966913 10162:PLOS ONE 10149:18285820 10094:Archived 10022: · 9910:16437551 9869:16464022 9834:11779493 9793:28423717 9744:33267773 9693:27629060 9636:20940144 9587:17616978 9533:15956212 9474:31963223 9420:26186941 9371:24108092 9322:22781841 9273:27251462 9238:15365186 9179:33171795 9128:31993111 9079:27251462 9039:24571128 8990:11353081 8938:21163908 8889:24336318 8840:28753428 8789:23622243 8740:25456125 8688:25707793 8631:23442605 8580:23762867 8529:14562054 8507:Oncogene 8488:12651607 8439:44644467 8431:15922863 8389:24590400 8348:15701830 8307:22165252 8299:16879693 8264:19010819 8215:22286769 8193:Oncogene 8174:23249749 8125:22956494 8062:22494821 8036:(1): 3. 8011:20351277 7952:15887099 7911:18733871 7903:23271133 7867:23422094 7818:21706233 7782:20653064 7731:16174854 7690:15888787 7598:21779515 7549:17616978 7498:18704159 7401:11850397 7352:16728433 7244:23671730 7190:21278452 7141:17412712 7100:12640109 7051:22082348 6994:16491070 6956:15125777 6905:24397478 6848:10688865 6804:16426080 6796:18323444 6753:11342123 6745:25907220 6694:17136093 6640:15829956 6597:14941857 6589:26667849 6544:25423595 6501:15829966 6458:26896565 6409:17683622 6293:10830948 6258:43118901 6250:14734635 6209:12547392 6173:33503081 6165:15205477 6114:11242085 6071:23363784 6014:15927235 5979:15858357 5937:16472827 5893:41930529 5885:11950998 5836:15105825 5787:16153173 5752:16464012 5717:17883408 5673:11833768 5632:12479224 5539:12556884 5488:16327781 5453:23045548 5401:17635991 5357:22531782 5308:14232192 5300:18001824 5213:18025084 5169:27568560 5117:27733626 5063:19502789 5014:23633913 4951:11425512 4890:21302943 4841:18616294 4792:19258535 4744:12643795 4707:17006450 4664:23565119 4613:25789972 4564:23610439 4502:16890458 4494:14744439 4434:32239214 4411:12954774 4362:15692565 4313:10438542 4117:16012167 4073:33154242 3982:16793370 3879:24722637 3800:19228922 3751:12797829 3701:19594328 3644:15664931 3636:17667954 3601:16460230 3566:16540631 3525:16940754 3410:10547702 3316:15589490 3271:53798180 3173:Progeria 3090:See also 3006:bacteria 2937:promoter 2924:promoter 2821:CpG site 2782:CpG site 2763:CpG site 2727:H3K36me3 2719:H3K36me3 2689:site is 2600:accurate 2565:microRNA 1943:Olaparib 1935:olaparib 1672:lymphoma 1575:protease 1548:operator 1305:protein 1170:proteins 1168:such as 1141:proteins 1070:AP sites 996:in vitro 884:(NHEJ), 857:E. coli 747:bacteria 664:Mutation 610:toxicity 586:histones 524:such as 441:cytosine 414:mismatch 327:aromatic 312:certain 244:histones 228:proteins 132:that is 10693:Biology 10508:SOS box 10260:AP site 10193:4788447 10170:Bibcode 10140:2262034 10009: ( 9980:minutes 9784:5522286 9735:7709351 9684:5024116 9663:Bibcode 9655:Sci Rep 9627:3000680 9578:1913100 9524:1157029 9501:Bibcode 9465:7016758 9411:4937888 9362:3858462 9313:3521964 9206:Bibcode 9170:7664663 9119:6974700 9030:3985951 8929:3043087 8880:4116484 8780:3641580 8731:4254608 8679:4425546 8658:Bibcode 8622:3599366 8571:3666359 8479:1851213 8255:2948671 8165:3543090 8116:3707278 8053:3351028 8002:2872463 7979:Bibcode 7826:8069716 7773:2909555 7681:1774551 7641:9353177 7621:Bibcode 7613:Science 7589:3135649 7540:1913100 7489:2491723 7442:5770175 7433:1706430 7392:1084010 7343:2612936 7303:9096356 7271:Bibcode 7235:3648662 7181:3030973 7042:3590802 7002:2514545 6896:4064942 6875:Bibcode 6776:Bibcode 6768:Science 6702:4406956 6674:Bibcode 6648:4398393 6620:Bibcode 6509:4391043 6481:Bibcode 6449:4811676 6400:1959234 6383:: 152. 6301:4402039 6145:Bibcode 6137:Science 6122:4356885 6094:Bibcode 6062:3615161 6022:7067036 5917:Bibcode 5863:Bibcode 5855:Science 5827:1299048 5547:4403303 5519:Bibcode 5496:9797133 5444:3471223 5348:3365417 5259:9488723 5160:5089070 5108:5170603 5054:3856216 5005:3468886 4881:3062377 4832:2646719 4783:2650891 4715:4412830 4687:Bibcode 4655:3613618 4604:4385936 4555:3651503 4532:Bibcode 4272:8890183 4223:8628283 4174:4422938 4166:9242411 4144:Bibcode 4065:5106728 4030:5055816 3871:3278898 3851:Bibcode 3791:2668831 3516:3488278 3462:Bibcode 3002:viruses 2800:enzyme 2569:miR-155 2497:genetic 2445:repair) 1396:kinases 1345:kinases 1276:histone 1125:E. coli 1081:factor 936:in the 827:ligase. 817:AP site 755:animals 630:divides 580:during 562:nucleus 488:cancer. 445:thymine 336:viruses 250:Sources 224:adducts 90:mitosis 10679:Portal 10633:FANCD2 10628:FANCD1 10388:RecBCD 10341:RAD23B 10336:RAD23A 10200: 10190: 10147: 10137: 10119:EMBO J 9941:about 9908: 9867: 9832: 9791: 9781: 9742: 9732: 9691: 9681: 9634: 9624: 9585: 9575: 9531: 9521: 9472: 9462: 9418: 9408: 9369: 9359: 9320: 9310: 9271: 9236: 9229:518826 9226: 9177: 9167: 9126: 9116: 9077: 9037: 9027: 8988: 8978: 8936: 8926: 8887: 8877: 8838: 8787: 8777: 8738: 8728: 8686: 8676: 8650:Nature 8629: 8619: 8605:: 90. 8578: 8568: 8527: 8486: 8476: 8437: 8429: 8387: 8346: 8305: 8297: 8262: 8252: 8213: 8172: 8162: 8123: 8113: 8103: 8060: 8050: 8009: 7999: 7950: 7909: 7901: 7865: 7824: 7816: 7780: 7770: 7729: 7688: 7678: 7639: 7596: 7586: 7547: 7537: 7496: 7486: 7440: 7430: 7399: 7389: 7350: 7340: 7301: 7291: 7242: 7232: 7188: 7178: 7139: 7098: 7091:150734 7088: 7049: 7039: 7000: 6992: 6954: 6947:419366 6944: 6903: 6893: 6846: 6802: 6794: 6751: 6743: 6700: 6692: 6666:Nature 6646: 6638: 6612:Nature 6595: 6587: 6542: 6507: 6499: 6473:Nature 6456: 6446: 6407: 6397: 6350: 6299: 6291: 6273:Nature 6256: 6248: 6207: 6171: 6163: 6120: 6112: 6086:Nature 6069: 6059: 6020: 6012: 5977: 5935: 5891: 5883: 5834: 5824: 5785: 5750: 5715: 5671: 5630: 5597: 5568: 5545: 5537: 5511:Nature 5494: 5486: 5451: 5441: 5399: 5355: 5345: 5306: 5298: 5257: 5211: 5167: 5157: 5115: 5105: 5061: 5051: 5012: 5002: 4949: 4888: 4878: 4839: 4829: 4790: 4780: 4742: 4713: 4705: 4679:Nature 4662: 4652: 4638:: 48. 4611: 4601: 4562: 4552: 4500: 4492: 4432: 4428:, 4409: 4402:203313 4399: 4360: 4353:549622 4350: 4311: 4270: 4263:452249 4260: 4221: 4214:231204 4211: 4172: 4164: 4136:Nature 4115: 4071: 4063: 4028: 4003: 3980: 3970: 3930: 3905: 3877: 3869: 3826: 3798: 3788: 3749: 3699: 3681: 3642: 3634: 3599: 3564: 3523: 3513: 3431: 3408: 3314: 3296: 3269: 3259: 3196:under 3084:CRISPR 3067:gamete 2507:or in 1890:Cancer 1692:humans 1495:cyclin 1426:, and 1180:, and 1178:lipids 1134:lesion 1101:using 1024:D-loop 994:In an 930:B-cell 892:(HR): 702:genome 658:cancer 512:purine 500:purine 317:toxins 298:x-rays 175:, and 98:cancer 62:genome 10648:FANCN 10643:FANCJ 10638:FANCI 10621:FANCM 10616:FANCL 10611:FANCG 10606:FANCF 10601:FANCE 10596:FANCC 10591:FANCB 10586:FANCA 10446:ERCC8 10441:ERCC6 10405:RAD51 10326:ERCC1 9442:Cells 8981:55450 8435:S2CID 8407:(PDF) 8303:S2CID 7907:S2CID 7822:S2CID 7294:20332 6998:S2CID 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