122:
227:
314:
305:). SLBP binding is required for efficient processing, export, and translation of histone mRNAs, allowing it to function as a highly sensitive biochemical "switch". During S-phase, accumulation of SLBP acts together with NPAT to drastically increase the efficiency of histone production. However, once S-phase ends, both SLBP and bound RNA are rapidly degraded. This immediately halts histone production and prevents a toxic buildup of free histones.
25:
322:
nucleosome octamers, resulting in the release of H3-H4 and H2A-H2B subunits. Reassembly of nucleosomes behind the replication fork is mediated by chromatin assembly factors (CAFs) that are loosely associated with replication proteins. Though not fully understood, the reassembly does not appear to utilize the
326:
scheme seen in DNA replication. Labeling experiments indicate that nucleosome duplication is predominantly conservative. The paternal H3-H4 core nucleosome remains completely segregated from newly synthesized H3-H4, resulting in the formation of nucleosomes that either contain exclusively old H3-H4
269:
Complete replication fork assembly and activation only occurs on a small subset of replication origins. All eukaryotes possess many more replication origins than strictly needed during one cycle of DNA replication. Redundant origins may increase the flexibility of DNA replication, allowing cells to
346:
However, for small domains approaching the size of individual genes, old nucleosomes are spread too thinly for accurate propagation of histone modifications. In these regions, chromatin structure is probably controlled by incorporation of histone variants during nucleosome reassembly. The close
364:
detects stalled replication forks by integrating signals from RPA, ATR Interacting
Protein (ATRIP), and RAD17. Upon activation, the replication checkpoint upregulates nucleotide biosynthesis and blocks replication initiation from unfired origins. Both of these processes contribute to rescue of
321:
Free histones produced by the cell during S-phase are rapidly incorporated into new nucleosomes. This process is closely tied to the replication fork, occurring immediately in “front” and “behind” the replication complex. Translocation of MCM helicase along the leading strand disrupts parental
290:, a nuclear coactivator of histone transcription. NPAT is activated by phosphorylation and recruits the Tip60 chromatin remodeling complex to the promoters of histone genes. Tip60 activity removes inhibitory chromatin structures and drives a three to ten-fold increase in transcription rate.
182:(R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. This transition is essentially irreversible; after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable.
413:
cells dramatically prolongs S-phase and causes permanent arrest in G2-phase. This unique arrest phenotype is not associated with activation of canonical DNA damage pathways, indicating that nucleosome assembly and histone supply may be scrutinized by a novel S-phase checkpoint.
335:
Immediately after division, each daughter chromatid only possesses half the epigenetic modifications present in the paternal chromatid. The cell must use this partial set of instructions to re-establish functional chromatin domains before entering mitosis.
249:
Activation of the pre-RC is a closely regulated and highly sequential process. After Cdc7 and S-phase CDKs phosphorylate their respective substrates, a second set of replicative factors associate with the pre-RC. Stable association encourages
355:
During S-phase, the cell continuously scrutinizes its genome for abnormalities. Detection of DNA damage induces activation of three canonical S-phase "checkpoint pathways" that delay or arrest further cell cycle progression:
343:) and several other histone-modifying complexes can "copy" modifications present on old histones onto new histones. This process amplifies epigenetic marks and counters the dilutive effect of nucleosome duplication.
372:
blocks mitosis until the entire genome has been successfully duplicated. This pathway induces arrest by inhibiting the Cyclin-B-CDK1 complex, which gradually accumulates throughout the cell cycle to promote mitotic
392:
kinases. In addition to facilitating DNA repair, active ATR and ATM stalls cell cycle progression by promoting degradation of CDC25A, a phosphatase that removes inhibitory phosphate residues from CDKs.
212:
transcription factor, which in turn initiates expression of S-phase genes. Several E2F target genes promote further release of E2F, creating a positive feedback loop similar to the one found in yeast.
409:
In addition to these canonical checkpoints, recent evidence suggests that abnormalities in histone supply and nucleosome assembly can also alter S-phase progression. Depletion of free histones in
185:
Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. In yeast, for instance, cell growth induces accumulation of Cln3
242:
distributed throughout the genome. During S-phase, the cell converts pre-RCs into active replication forks to initiate DNA replication. This process depends on the kinase activity of
347:
correlation seen between H3.3/H2A.Z and transcriptionally active regions lends support to this proposed mechanism. Unfortunately, a causal relationship has yet to be proven.
164:. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved.
339:
For large genomic regions, inheritance of old H3-H4 nucleosomes is sufficient for accurate re-establishment of chromatin domains. Polycomb
Repressive Complex 2 (
327:
or exclusively new H3-H4. “Old” and “new” histones are assigned to each daughter strand semi-randomly, resulting in equal division of regulatory modifications.
792:"Stem-loop binding protein, the protein that binds the 3' end of histone mRNA, is cell cycle regulated by both translational and posttranslational mechanisms"
689:"Transcriptional activation of histone genes requires NPAT-dependent recruitment of TRRAP-Tip60 complex to histone promoters during the G1/S phase transition"
208:
signals received throughout G1-phase cause gradual accumulation of cyclin D, which complexes with CDK4/6. Active cyclin D-CDK4/6 complex induces release of
432:
1199:
428:
243:
293:
In addition to increasing transcription of histone genes, S-phase entry also regulates histone production at the RNA level. Instead of
1491:
1385:
1431:
470:
263:
89:
1192:
108:
61:
266:
sliding clamps. Loading of these factors completes the active replication fork and initiates synthesis of new DNA.
254:
to unwind a small stretch of parental DNA into two strands of ssDNA, which in turn recruits replication protein A (
193:
CDK2. The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating the transcriptional repressor
68:
46:
121:
1185:
323:
286:
proteins occurs alongside DNA replication. During early S-phase, the cyclin E-Cdk2 complex phosphorylates
1501:
75:
258:), an ssDNA binding protein. RPA recruitment primes the replication fork for loading of replicative DNA
1642:
1345:
1078:"DNA repair by nonhomologous end joining and homologous recombination during cell cycle in human cells"
251:
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201:, this pathway creates a positive feedback loop that fully commits cells to S-phase gene expression.
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35:
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double-strand breaks, is most active in S phase, declines in G2/M and is nearly absent in
8:
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Bartek J, Lukas C, Lukas J (October 2004). "Checking on DNA damage in S phase".
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857:
790:
Whitfield ML, Zheng LX, Baldwin A, Ohta T, Hurt MM, Marzluff WF (June 2000).
480:
317:
Conservative reassembly of core H3/H4 nucleosome behind the replication fork.
841:"How the cell cycle impacts chromatin architecture and influences cell fate"
246:
and various S-phase CDKs, both of which are upregulated upon S-phase entry.
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979:"Split decision: what happens to nucleosomes during DNA replication?"
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control the rate of DNA synthesis and respond to replication stress.
1132:"Histone supply regulates S phase timing and cell cycle progression"
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24:
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1543:
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197:. Since upregulation of S-phase genes drive further suppression of
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A remarkably similar regulatory scheme exists in mammalian cells.
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DNA replication phase of the cell cycle, between G1 and G2 phase
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Mao Z, Bozzella M, Seluanov A, Gorbunova V (September 2008).
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529:"Control of cell cycle transcription during G1 and S phases"
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DeRan M, Pulvino M, Greene E, Su C, Zhao J (January 2008).
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to function properly, synthesis of canonical (non-variant)
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motif that selective binds to Stem Loop
Binding Protein (
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Throughout M phase and G1 phase, cells assemble inactive
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141:
125:
Asymmetry in the synthesis of leading and lagging strands
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330:
297:, canonical histone transcripts possess a conserved 3`
1129:
365:
stalled forks by increasing the availability of dNTPs.
838:
912:
686:
1130:Günesdogan U, Jäckle H, Herzig A (September 2014).
527:Bertoli C, Skotheim JM, de Bruin RA (August 2013).
49:. Unsourced material may be challenged and removed.
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591:"DNA replication and progression through S phase"
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463:The cell cycle : principles of control
178:Entry into S-phase is controlled by the G1
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913:Ramachandran S, Henikoff S (August 2015).
639:Cold Spring Harbor Perspectives in Biology
1492:Cellular apoptosis susceptibility protein
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109:Learn how and when to remove this message
839:Ma Y, Kanakousaki K, Buttitta L (2015).
741:Marzluff WF, Koreski KP (October 2017).
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500:The Restriction Point of the Cell Cycle
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633:Leonard AC, MĂ©chali M (October 2013).
533:Nature Reviews. Molecular Cell Biology
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331:Reestablishment of chromatin domains
278:Since new DNA must be packaged into
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47:adding citations to reliable sources
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983:The Journal of Biological Chemistry
497:Pardee AB, Blagosklonny MV (2013).
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743:"Birth and Death of Histone mRNAs"
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589:Takeda DY, Dutta A (April 2005).
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808:10.1128/MCB.20.12.4188-4198.2000
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34:needs additional citations for
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796:Molecular and Cellular Biology
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693:Molecular and Cellular Biology
435:(oncology/pathology prognosis)
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384:(DSBs) through activation of
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977:Annunziato AT (April 2005).
7:
1502:Maturation promoting factor
651:10.1101/cshperspect.a010116
465:. Oxford University Press.
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189:, which complexes with the
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1643:Postreplication checkpoint
397:, an accurate process for
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915:"Replicating Nucleosomes"
759:10.1016/j.tig.2017.07.014
635:"DNA replication origins"
236:pre-replication complexes
858:10.3389/fgene.2015.00019
395:Homologous recombination
378:intra-S Phase Checkpoint
191:cyclin dependent kinase
1625:Cell cycle checkpoints
996:10.1074/jbc.R400039200
939:10.1126/sciadv.1500587
608:10.1038/sj.onc.1208616
362:Replication Checkpoint
351:DNA damage checkpoints
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309:Nucleosome replication
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230:Steps in DNA synthesis
136:) is the phase of the
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1652:Other cellular phases
1376:CDK-activating kinase
845:Frontiers in Genetics
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1094:10.4161/cc.7.18.6679
705:10.1128/MCB.00607-07
503:. Landes Bioscience.
382:Double Strand Breaks
295:polyadenylated tails
148:, occurring between
43:improve this article
1149:10.7554/eLife.02443
931:2015SciA....1E0587R
424:S phase index (SPI)
240:replication origins
1638:Spindle checkpoint
1443:P53 p63 p73 family
747:Trends in Genetics
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439:Restriction point
324:semi-conservative
274:Histone synthesis
180:restriction point
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461:David M (2007).
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1041:(10): 792–804.
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989:(13): 12065–8.
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925:(7): e1500587.
911:
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837:
833:
802:(12): 4188–98.
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753:(10): 745–759.
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645:(10): a010116.
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601:(17): 2827–43.
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32:This article
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1594:Prometaphase
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252:MCM helicase
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238:(pre-RC) on
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41:Please help
36:verification
33:
1615:Cytokinesis
1584:Preprophase
1528:checkpoints
280:nucleosomes
260:polymerases
1698:Cell cycle
1536:Interphase
1526:Phases and
1209:Cell cycle
1142:: e02443.
1082:Cell Cycle
445:References
429:S-fraction
411:Drosophila
168:Regulation
146:replicated
138:cell cycle
69:newspapers
1659:Apoptosis
1609:Telophase
1599:Metaphase
1394:INK4a/ARF
481:813540567
299:stem loop
206:Mitogenic
140:in which
58:"S phase"
1692:Category
1604:Anaphase
1589:Prophase
1212:proteins
1168:25205668
1112:18769152
1063:33560392
1055:15459660
1005:15664979
957:26269799
877:25691891
826:10825184
777:28867047
723:17967892
669:23838439
617:15838518
595:Oncogene
563:23877564
418:See also
403:G1 phase
380:detects
1673:Meiosis
1580:Mitosis
1572:M phase
1553:S phase
1420:cip/kip
1159:4157229
1103:2754209
948:4530793
927:Bibcode
868:4315090
768:5645032
714:2223310
660:3783049
554:4569015
284:histone
130:S phase
83:scholar
1512:Cullin
1398:p14arf
1220:Cyclin
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1548:phase
1487:Cdc42
1482:Cdc25
1470:Other
1252:, B3)
1136:eLife
1059:S2CID
817:85788
162:phase
154:phase
90:JSTOR
76:books
1516:CUL7
1477:Cdc2
1164:PMID
1108:PMID
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953:PMID
873:PMID
822:PMID
773:PMID
719:PMID
665:PMID
613:PMID
559:PMID
477:OCLC
467:ISBN
388:and
376:The
368:The
360:The
341:PRC2
303:SLBP
288:NPAT
264:PCNA
262:and
244:Cdc7
199:Whi5
195:Whi5
156:and
62:news
1507:Wee
1497:E2F
1461:p73
1456:p63
1451:p53
1432:p57
1428:p27
1424:p21
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1410:p18
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1293:CDK
1154:PMC
1144:doi
1098:PMC
1090:doi
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991:doi
987:280
943:PMC
935:doi
863:PMC
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812:PMC
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763:PMC
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709:PMC
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647:doi
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549:PMC
541:doi
431:or
390:ATM
386:ATR
256:RPA
210:E2F
144:is
142:DNA
45:by
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