63:
173:. Nicking endonucleases introduce the strand discontinuities, or DNA nicks, for both respective systems. Mut L homologues from eukaryotes and most bacteria incise the discontinuous strand to introduce the entry or termination point for the excision reaction. Similarly, in E. coli, Mut H nicks the unmethylated strand of the duplex to introduce the entry point of excision. For eukaryotes specifically, the mechanism of DNA replication elongation between the leading and lagging strand differs. On the lagging strand, nicks exist between
106:
234:
preferentially acts at nicks in DNA to cleave adjacent to the nick and then winds or unwinds the complex topologies associated with packed DNA. Here, the nick in the DNA serves as a marker for single strand breakage and subsequent unwinding. It is possible that this is not a highly conserved process.
71:
Nicked DNA can be the result of DNA damage or purposeful, regulated biomolecular reactions carried out in the cell. During processing, DNA can be nicked by physical shearing, over-drying or enzymes. Excessive rough handling in pipetting or vortexing creates physical stress that can lead to breaks and
76:
can assist with this process. A single-stranded break (nick) in DNA can be formed by the hydrolysis and subsequent removal of a phosphate group within the helical backbone. This leads to a different DNA conformation, where a hydrogen bond forms in place of the missing piece of the DNA backbone in
66:
The diagram shows the effects of nicks on intersecting DNA forms. A plasmid is tightly wound into a negative supercoil (a). To release the intersecting states, the torsional energy must be released by utilizing nicks (b). After introducing a nick in the system, the negative supercoil gradually
138:
Ligases have a metal binding site which is capable of recognizing nicks in DNA. The ligase forms a DNA-adenylate complex, assisting recognition. With human DNA ligase, this forms a crystallized complex. The complex, which has a DNA–adenylate intermediate, allows
235:
Topoisomerase may cause short deletions when it cleaves bonds, because both full-length DNA products and short deletion strands are seen as products of topoisomerase cleavage while inactive mutants only produced full-length DNA strands.
265:, therefore nick idling plays a role in stalling the complex as it replicates in the reverse direction in small fragments (Okazaki fragments) and has to stop and reposition itself in between each and every fragment length of DNA.
160:(MMR) is an important DNA repair system that helps maintain genome plasticity by correcting mismatches, or non Watson-Crick base pairs in the a DNA duplex. Some sources of mismatched base pairs include replication errors and
92:
that join the 3’ hydroxyl and 5’ phosphate ends to form a phosphodiester bond, making them essential in nicked DNA repair, and ultimately genome fidelity. This biological role has also been extremely valuable in sealing the
211:
and then adding the nicked DNA to an environment rich in DNA polymerase and tagged nucleotide. The DNA polymerase then replaces the DNA nucleotides with the tagged ones, starting at the site of the single-stranded nick.
168:
is directed to the erroneous strand of the mismatched duplex through recognition of strand discontinuities, while MMR in E. coli and closely related bacteria is directed to the strand on the basis of the absence of
97:
of plasmids in molecular cloning. Their importance is attested by the fact most organisms have multiple ligases dedicated to specific pathways of repairing DNA. In eubacteria these ligases are powered by
156:
Single-stranded nicks act as recognizable markers to help the repair machinery distinguish the newly synthesized strand (daughter strand) from the template strand (parental strand).
342:
at the nic site. The cleaved strand is left with a hydroxyl group at the 3' end, which may allow for the strand to form a circular plasmid after moving into the recipient cell.
1206:
Gioia M, Payero L, Salim S, Fajish VG, Farnaz AF, Pannafino G, Chen JJ, Ajith VP, Momoh S, Scotland M, Raghavan V, Manhart CM, Shinohara A, Nishant KT, Alani E (April 2023).
276:, as the built up stress from twisting and packing is not being resisted as strongly anymore. Nicked DNA is more susceptible to degradation due to this reduced stability.
220:
Nicked DNA plays an important role in many biological functions. For instance, single-stranded nicks in DNA may serve as purposeful biological markers for the enzyme
776:
Pascal, John M.; O'Brien, Patrick J.; Tomkinson, Alan E.; Ellenberger, Tom (2004). "Human DNA ligase I completely encircles and partially unwinds nicked DNA".
135:
NAD+ dependent DNA ligase, LigA. LigA is a relevant example as it is structurally similar to a clade of enzymes found across all types of bacteria.
672:
249:
Nick idling is a biological process in which DNA polymerase may slow or stop its activity of adding bases to a new daughter strand during
189:. Together, the presence of a nick and a ribonucleotide make the leading strand easily recognizable to the DNA mismatch repair machinery.
181:. Due to the continuous replication that occurs on the leading strand, the mechanism there is slightly more complex. During replication,
59:. Nicking can be used to dissipate the energy held up by intersecting states. The nicks allow the DNA to take on a circular shape.
203:
must repair the final segment of DNA backbone in order to complete the repair process. In a lab setting, this can be used to introduce
836:
908:"Topoisomerase I alone is sufficient to produce short DNA deletions and can also reverse nicks at ribonucleotide sites"
99:
1110:"Characterization of the reaction product of the oriT nicking reaction catalyzed by Escherichia coli DNA helicase I"
737:"Crystal Structure of Eukaryotic DNA Ligase–Adenylate Illuminates the Mechanism of Nick Sensing and Strand Joining"
539:
Timson, David J; Singleton, Martin R; Wigley, Dale B (2000). "DNA ligases in the repair and replication of DNA".
238:
Nicks in DNA also give rise to different structural properties, can be involved in repairing damages caused by
199:
to excise and replace possibly damaged nucleotides. At the end of the segment that DNA polymerase acts on,
178:
967:"Generation of supercoils in nicked and gapped DNA drives DNA unknotting and postreplicative decatenation"
268:
DNA structure changes when a single-stranded nick is introduced. Stability is decreased as a break in the
43:
action. Nicks allow DNA strands to untwist during replication, and are also thought to play a role in the
143:
to institute a conformational change in the DNA for the isolation and subsequent repair of the DNA nick.
261:
in double stranded DNA replication because the direction of replication is opposite to the direction of
319:. Before this cleavage can occur, however, it is necessary for a group of proteins to attach to the
351:
72:
nicks in DNA. Overdrying of DNA can also break the phosphodiester bond in DNA and result in nicks.
269:
207:
or other tagged nucleotides by purposefully inducing site-specific, single-stranded nicks in DNA
118:
688:"Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate"
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Racko, Dusan; Benedetti, Fabrizio; Dorier, Julien; Burnier, Yannis; Stasiak, Andrzej (2015).
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and transcription. In these instances, nicked DNA is not the result of unwanted cell damage.
62:
785:
486:
473:
Aymami, J.; Coll, M.; Marel, G. A. van der; Boom, J. H. van; Wang, A. H.; Rich, A. (1990).
315:. This single strand is eventually transferred to the recipient cell during the process of
231:
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site. This group of proteins is called the relaxosome. It is thought that portions of the
185:
are added by replication enzymes and these ribonucleotides are nicked by an enzyme called
8:
339:
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36:
28:
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site are bent in a way that creates interaction between the relaxosome proteins and the
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1208:"Exo1 protects DNA nicks from ligation to promote crossover formation during meiosis"
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is a biological process in which a single-stranded DNA nick serves as the marker for
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rather than ATP. Each nick site requires 1 ATP or 1 NAD+ to power the ligase repair.
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Lanka E, Wilkins BM (1995). "DNA processing reactions in bacterial conjugation".
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In order to join these fragments, the ligase progresses through three steps:
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mechanisms that fix errors on both the leading and lagging daughter strands.
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Odell, Mark; Sriskanda, Verl; Shuman, Stewart; Nikolov, Dimitar B. (2000).
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and are easily recognizable by the DNA mismatch repair machinery prior to
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686:
Nandakumar, Jayakrishnan; Nair, Pravin A.; Shuman, Stewart (2007-04-27).
239:
161:
94:
797:
439:"Configuration Transitions of Free Circular DNA System Induced by Nicks"
55:
The diagram shows the effects of nicks on intersecting DNA in a twisted
475:"Molecular structure of nicked DNA: a substrate for DNA repair enzymes"
200:
32:
625:"Chlorella virus DNA ligase: nick recognition and mutational analysis"
775:
165:
906:
Huang, Shar-Yin Naomi; Ghosh, Sanchari; Pommier, Yves (2015-05-29).
67:
unwinds (c) until it reaches its final, circular, plasmid state (d).
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208:
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of 5-methylcytosine DNA to form thymine. MMR in most bacteria and
131:
One particular example of a ligase catalyzing nick closure is the
355:
56:
89:
85:
40:
576:"Eukaryotic DNA ligases: structural and functional insights"
242:
radiation, and are used in the primary steps that allow for
964:
734:
573:
385:"Ribonucleotides in DNA: origins, repair and consequences"
24:
1159:"Conjugative plasmid transfer in gram-positive bacteria"
215:
121:(AMP) group to the enzyme, referred to as adenylylation,
109:
Minimalistic mechanism of DNA nick sealing by DNA ligase
1205:
827:
Morris, James (2013). "14. Mutations and DNA Repair".
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253:at a nick site. This is particularly relevant to
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854:"DNA Mismatch Repair in Eukaryotes and Bacteria"
358:, and such nicks are protected from ligation by
567:
479:Proceedings of the National Academy of Sciences
437:Ji, Chao; Zhang, Lingyun; Wang, Pengye (2015).
127:Nick sealing, or phosphodiester bond formation.
124:Adenosine monophosphate transfer to the DNA and
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616:
1157:Grohmann E, Muth G, Espinosa M (June 2003).
1108:Matson SW, Nelson WC, Morton BS (May 1993).
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671:: CS1 maint: DOI inactive as of July 2024 (
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224:that unwinds packed DNA and is critical to
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1019:"Flexibility and stiffness in nicked DNA"
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592:10.1146/annurev.biochem.77.061306.123941
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23:is a discontinuity in a double stranded
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1017:Hays, J. B.; Zimm, B. H. (1970-03-14).
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623:Sriskanda V, Shuman S (January 1998).
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303:. A single strand of DNA, called the
216:Role in replication and transcription
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574:Ellenberger T, Tomkinson AE (2008).
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468:
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383:Williams JS, Kunkel TA (July 2014).
1087:10.1146/annurev.bi.64.070195.001041
912:The Journal of Biological Chemistry
291:or nick region is found within the
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77:order to preserve the structure.
299:) site and is a key in starting
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1126:10.1128/jb.175.9.2599-2606.1993
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334:Cleaving the T-strand involves
1175:10.1128/MMBR.67.2.277-301.2003
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1:
754:10.1016/S1097-2765(00)00115-5
553:10.1016/S0921-8777(00)00033-1
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88:are versatile and ubiquitous
1225:10.1371/journal.pbio.3002085
1036:10.1016/0022-2836(70)90162-2
1023:Journal of Molecular Biology
705:10.1016/j.molcel.2007.02.026
541:Mutation Research/DNA Repair
401:10.1016/j.dnarep.2014.03.029
74:Nicking endonuclease enzymes
39:typically through damage or
7:
27:molecule where there is no
16:Discontinuity in DNA strand
10:
1279:
858:Journal of Nucleic Acids
443:Journal of Nanomaterials
925:10.1074/jbc.M115.653345
829:Biology: How Life Works
643:(inactive 2024-07-02).
270:phosphodiester backbone
152:Role in mismatch repair
147:Biological implications
119:adenosine monophosphate
1163:Microbiol Mol Biol Rev
971:Nucleic Acids Research
500:10.1073/pnas.87.7.2526
110:
68:
852:Fukui, Kenji (2010).
317:bacterial conjugation
301:bacterial conjugation
244:genetic recombination
108:
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641:10.1093/nar/26.2.525
311:by an enzyme called
871:10.4061/2010/260512
798:10.1038/nature03082
790:2004Natur.432..473P
491:1990PNAS...87.2526A
456:10.1155/2015/546851
352:crossover formation
340:phosphodiester bond
158:DNA mismatch repair
45:DNA mismatch repair
29:phosphodiester bond
983:10.1093/nar/gkv683
580:Annu. Rev. Biochem
350:DNA nicks promote
293:origin of transfer
111:
69:
51:Formation of nicks
838:978-1-319-05691-9
629:Nucleic Acids Res
389:DNA Repair (Amst)
255:Okazaki fragments
175:Okazaki fragments
31:between adjacent
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193:Nick translation
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346:Role in meiosis
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251:DNA replication
232:Topoisomerase-1
226:DNA replication
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183:ribonucleotides
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117:Addition of an
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81:Repair of nicks
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747:(5): 1183–93.
741:Molecular Cell
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485:(7): 2526–30.
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263:DNA polymerase
259:lagging strand
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141:DNA ligase I
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1114:J Bacteriol
280:In bacteria
240:ultraviolet
205:fluorescent
171:methylation
162:deamination
95:sticky ends
33:nucleotides
1081:: 141–69.
586:: 313–38.
366:References
338:cutting a
201:DNA ligase
166:eukaryotes
1212:PLOS Biol
1045:0022-2836
934:1083-351X
714:1097-2765
395:: 27–37.
1257:Category
1244:37079643
1235:10153752
1193:12794193
1001:26150424
952:25887397
890:20725617
864:: 1–16.
806:15565146
763:11106756
722:17466627
610:18518823
561:10946235
419:24794402
362:(Exo1).
336:relaxase
313:relaxase
305:T-strand
209:in vitro
187:RNase H2
179:ligation
1144:8386720
1095:7574478
1053:5448592
992:4551925
943:4447978
881:2915661
814:3105417
786:Bibcode
659:9421510
601:2933818
519:2320572
487:Bibcode
410:4065383
356:meiosis
354:during
272:allows
133:E. coli
90:enzymes
86:Ligases
57:plasmid
35:of one
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331:site.
41:enzyme
37:strand
810:S2CID
510:53722
1240:PMID
1189:PMID
1140:PMID
1091:PMID
1049:PMID
1041:ISSN
997:PMID
948:PMID
930:ISSN
886:PMID
862:2010
833:ISBN
802:PMID
759:PMID
718:PMID
710:ISSN
673:link
655:PMID
606:PMID
557:PMID
515:PMID
447:2015
415:PMID
325:oriT
321:oriT
297:oriT
289:site
284:The
100:NAD+
21:nick
1263:DNA
1230:PMC
1220:doi
1179:PMC
1171:doi
1130:PMC
1122:doi
1118:175
1083:doi
1031:doi
987:PMC
979:doi
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920:doi
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876:PMC
866:doi
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782:432
749:doi
700:doi
645:PMC
637:doi
596:PMC
588:doi
549:doi
545:460
505:PMC
495:doi
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