Critical Function of γH2A in S-Phase
ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3 related) are evolutionary conserved protein kinases that phosphorylate the carboxyl-tail of histone H2AX in chromatin flanking DNA lesions. Phosphorylated histone H2AX (aka γH2AX) tethers important DNA damage response (DDR) proteins to DNA double-strand breaks but its function during DNA replication is unclear. A novel genetic screen reveals that a partial defect in Replication Factor C (RFC) creates a critical requirement for γH2AX in fission yeast. These studies indicate that γH2AX stabilizes replication forks by recruiting Brc1 when RFC is unable to load the DNA clamp known as proliferating cell nuclear antigen (PCNA) onto duplex DNA. Surprisingly, this activity of γH2AX is more critical than ATM/ATR-mediated activation of the checkpoint kinase Chk1 and Chk2.
Vyšlo v časopise:
Critical Function of γH2A in S-Phase. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005517
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1005517
Souhrn
ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3 related) are evolutionary conserved protein kinases that phosphorylate the carboxyl-tail of histone H2AX in chromatin flanking DNA lesions. Phosphorylated histone H2AX (aka γH2AX) tethers important DNA damage response (DDR) proteins to DNA double-strand breaks but its function during DNA replication is unclear. A novel genetic screen reveals that a partial defect in Replication Factor C (RFC) creates a critical requirement for γH2AX in fission yeast. These studies indicate that γH2AX stabilizes replication forks by recruiting Brc1 when RFC is unable to load the DNA clamp known as proliferating cell nuclear antigen (PCNA) onto duplex DNA. Surprisingly, this activity of γH2AX is more critical than ATM/ATR-mediated activation of the checkpoint kinase Chk1 and Chk2.
Zdroje
1. Cimprich KA, Cortez D (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9: 616–627. doi: 10.1038/nrm2450 18594563
2. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461: 1071–1078. doi: 10.1038/nature08467 19847258
3. Bonner WM, Redon CE, Dickey JS, Nakamura AJ, Sedelnikova OA, et al. (2008) GammaH2AX and cancer. Nat Rev Cancer 8: 957–967. doi: 10.1038/nrc2523 19005492
4. Stucki M, Jackson SP (2006) gammaH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair (Amst) 5: 534–543.
5. Celeste A, Petersen S, Romanienko PJ, Fernandez-Capetillo O, Chen HT, et al. (2002) Genomic instability in mice lacking histone H2AX. Science 296: 922–927. 11934988
6. Downs JA, Lowndes NF, Jackson SP (2000) A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature 408: 1001–1004. 11140636
7. Nakamura TM, Du LL, Redon C, Russell P (2004) Histone H2A phosphorylation controls Crb2 recruitment at DNA breaks, maintains checkpoint arrest, and influences DNA repair in fission yeast. Mol Cell Biol 24: 6215–6230. 15226425
8. Rozenzhak S, Mejia-Ramirez E, Williams JS, Schaffer L, Hammond JA, et al. (2010) Rad3 decorates critical chromosomal domains with gammaH2A to protect genome integrity during S-Phase in fission yeast. PLoS Genet 6: e1001032. doi: 10.1371/journal.pgen.1001032 20661445
9. Szilard RK, Jacques PE, Laramee L, Cheng B, Galicia S, et al. (2010) Systematic identification of fragile sites via genome-wide location analysis of gamma-H2AX. Nat Struct Mol Biol 17: 299–305. doi: 10.1038/nsmb.1754 20139982
10. Williams JS, Williams RS, Dovey CL, Guenther G, Tainer JA, et al. (2010) gammaH2A binds Brc1 to maintain genome integrity during S-phase. EMBO J 29: 1136–1148. doi: 10.1038/emboj.2009.413 20094029
11. Bass KL, Murray JM, O'Connell MJ (2012) Brc1-dependent recovery from replication stress. J Cell Sci 125: 2753–2764. doi: 10.1242/jcs.103119 22366461
12. Shimada M, Okuzaki D, Tanaka S, Tougan T, Tamai KK, et al. (1999) Replication factor C3 of Schizosaccharomyces pombe, a small subunit of replication factor C complex, plays a role in both replication and damage checkpoints. Mol Biol Cell 10: 3991–4003. 10588638
13. Indiani C, O'Donnell M (2006) The replication clamp-loading machine at work in the three domains of life. Nature reviews Molecular cell biology 7: 751–761. 16955075
14. Johnson A, O'Donnell M (2005) Cellular DNA replicases: components and dynamics at the replication fork. Annu Rev Biochem 74: 283–315. 15952889
15. Kim J, Robertson K, Mylonas KJ, Gray FC, Charapitsa I, et al. (2005) Contrasting effects of Elg1-RFC and Ctf18-RFC inactivation in the absence of fully functional RFC in fission yeast. Nucleic Acids Res 33: 4078–4089. 16040599
16. Navadgi-Patil VM, Burgers PM (2009) A tale of two tails: activation of DNA damage checkpoint kinase Mec1/ATR by the 9-1-1 clamp and by Dpb11/TopBP1. DNA Repair (Amst) 8: 996–1003.
17. Griffiths DJ, Barbet NC, McCready S, Lehmann AR, Carr AM (1995) Fission yeast rad17: a homologue of budding yeast RAD24 that shares regions of sequence similarity with DNA polymerase accessory proteins. EMBO J 14: 5812–5823. 8846774
18. Ansbach AB, Noguchi C, Klansek IW, Heidlebaugh M, Nakamura TM, et al. (2008) RFCCtf18 and the Swi1-Swi3 complex function in separate and redundant pathways required for the stabilization of replication forks to facilitate sister chromatid cohesion in Schizosaccharomyces pombe. Mol Biol Cell 19: 595–607. 18045993
19. Redon C, Pilch DR, Rogakou EP, Orr AH, Lowndes NF, et al. (2003) Yeast histone 2A serine 129 is essential for the efficient repair of checkpoint-blind DNA damage. EMBO Rep 4: 678–684. 12792653
20. Pommier Y (2006) Topoisomerase I inhibitors: camptothecins and beyond. Nat Rev Cancer 6: 789–802. 16990856
21. Wei Y, Wang HT, Zhai Y, Russell P, Du LL (2014) Mdb1, a fission yeast homolog of human MDC1, modulates DNA damage response and mitotic spindle function. PLoS One 9: e97028. doi: 10.1371/journal.pone.0097028 24806815
22. Kilkenny ML, Dore AS, Roe SM, Nestoras K, Ho JC, et al. (2008) Structural and functional analysis of the Crb2-BRCT2 domain reveals distinct roles in checkpoint signaling and DNA damage repair. Genes & development 22: 2034–2047.
23. Saka Y, Esashi F, Matsusaka T, Mochida S, Yanagida M (1997) Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1. Genes & development 11: 3387–3400.
24. Willson J, Wilson S, Warr N, Watts FZ (1997) Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene required for the DNA damage checkpoint but not the replication checkpoint. Nucleic Acids Res 25: 2138–2146. 9153313
25. Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, et al. (2004) Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119: 603–614. 15550243
26. Du LL, Nakamura TM, Russell P (2006) Histone modification-dependent and-independent pathways for recruitment of checkpoint protein Crb2 to double-strand breaks. Genes Dev 20: 1583–1596. 16778077
27. Sofueva S, Du LL, Limbo O, Williams JS, Russell P (2010) BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at double-strand breaks and maintain the DNA damage checkpoint. Mol Cell Biol 30: 4732–4743. doi: 10.1128/MCB.00413-10 20679485
28. Moser BA, Chang YT, Kosti J, Nakamura TM (2011) Tel1ATM and Rad3ATR kinases promote Ccq1-Est1 interaction to maintain telomeres in fission yeast. Nat Struct Mol Biol 18: 1408–1413. doi: 10.1038/nsmb.2187 22101932
29. Limbo O, Porter-Goff ME, Rhind N, Russell P (2011) Mre11 nuclease activity and Ctp1 regulate Chk1 activation by Rad3ATR and Tel1ATM checkpoint kinases at double-strand breaks. Molecular and cellular biology 31: 573–583. doi: 10.1128/MCB.00994-10 21098122
30. Enoch T, Carr AM, Nurse P (1992) Fission yeast genes involved in coupling mitosis to completion of DNA replication. Genes Dev 6: 2035–2046. 1427071
31. Furuya K, Poitelea M, Guo L, Caspari T, Carr AM (2004) Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes & development 18: 1154–1164.
32. Rhind N, Russell P (2000) Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. J Cell Sci 113 (Pt 22): 3889–3896. 11058076
33. Ohouo PY, Bastos de Oliveira FM, Liu Y, Ma CJ, Smolka MB (2013) DNA-repair scaffolds dampen checkpoint signalling by counteracting the adaptor Rad9. Nature 493: 120–124. doi: 10.1038/nature11658 23160493
34. Cussiol JR, Jablonowski CM, Yimit A, Brown GW, Smolka MB (2015) Dampening DNA damage checkpoint signalling via coordinated BRCT domain interactions. EMBO J 34: 1704–1717. doi: 10.15252/embj.201490834 25896509
35. Roseaulin L, Yamada Y, Tsutsui Y, Russell P, Iwasaki H, et al. (2008) Mus81 is essential for sister chromatid recombination at broken replication forks. EMBO J 27: 1378–1387. doi: 10.1038/emboj.2008.65 18388861
36. McGlynn P, Lloyd RG (2002) Recombinational repair and restart of damaged replication forks. Nat Rev Mol Cell Biol 3: 859–870. 12415303
37. Langerak P, Mejia-Ramirez E, Limbo O, Russell P (2011) Release of Ku and MRN from DNA ends by Mre11 nuclease activity and Ctp1 is required for homologous recombination repair of double-strand breaks. PLoS Genetics 7: e1002271. doi: 10.1371/journal.pgen.1002271 21931565
38. Williams RS, Dodson GE, Limbo O, Yamada Y, Williams JS, et al. (2009) Nbs1 flexibly tethers Ctp1 and Mre11-Rad50 to coordinate DNA double-strand break processing and repair. Cell 139: 87–99. doi: 10.1016/j.cell.2009.07.033 19804755
39. Boddy MN, Gaillard PH, McDonald WH, Shanahan P, Yates JR 3rd, et al. (2001) Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107: 537–548. 11719193
40. Noguchi E, Noguchi C, Du LL, Russell P (2003) Swi1 prevents replication fork collapse and controls checkpoint kinase Cds1. Mol Cell Biol 23: 7861–7874. 14560029
41. Yin L, Locovei AM, D'Urso G (2008) Activation of the DNA damage checkpoint in mutants defective in DNA replication initiation. Mol Biol Cell 19: 4374–4382. doi: 10.1091/mbc.E08-01-0020 18667534
42. Lemoine FJ, Degtyareva NP, Lobachev K, Petes TD (2005) Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites. Cell 120: 587–598. 15766523
43. Li X, Liu K, Li F, Wang J, Huang H, et al. (2012) Structure of C-terminal tandem BRCT repeats of Rtt107 protein reveals critical role in interaction with phosphorylated histone H2A during DNA damage repair. J Biol Chem 287: 9137–9146. doi: 10.1074/jbc.M111.311860 22262834
44. Ohouo PY, Bastos de Oliveira FM, Almeida BS, Smolka MB (2010) DNA damage signaling recruits the Rtt107-Slx4 scaffolds via Dpb11 to mediate replication stress response. Mol Cell 39: 300–306. doi: 10.1016/j.molcel.2010.06.019 20670896
45. Tomita K, Matsuura A, Caspari T, Carr AM, Akamatsu Y, et al. (2003) Competition between the Rad50 complex and the Ku heterodimer reveals a role for Exo1 in processing double-strand breaks but not telomeres. Mol Cell Biol 23: 5186–5197. 12861005
46. Limbo O, Chahwan C, Yamada Y, de Bruin RA, Wittenberg C, et al. (2007) Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control double-strand break repair by homologous recombination. Mol Cell 28: 134–146. 17936710
47. Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH, et al. (2013) ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 155: 1088–1103. doi: 10.1016/j.cell.2013.10.043 24267891
48. Lee KY, Myung K (2008) PCNA modifications for regulation of post-replication repair pathways. Mol Cells 26: 5–11. 18525240
49. Ulrich HD (2009) Regulating post-translational modifications of the eukaryotic replication clamp PCNA. DNA Repair (Amst) 8: 461–469.
50. Sheedy DM, Dimitrova D, Rankin JK, Bass KL, Lee KM, et al. (2005) Brc1-mediated DNA repair and damage tolerance. Genetics 171: 457–468. 15972456
51. Lee KM, Nizza S, Hayes T, Bass KL, Irmisch A, et al. (2007) Brc1-mediated rescue of Smc5/6 deficiency: requirement for multiple nucleases and a novel Rad18 function. Genetics 175: 1585–1595. 17277362
52. Rouse J (2004) Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J 23: 1188–1197. 14988729
53. Roberts TM, Kobor MS, Bastin-Shanower SA, Ii M, Horte SA, et al. (2006) Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. Mol Biol Cell 17: 539–548. 16267268
54. Balint A, Kim T, Gallo D, Cussiol JR, Bastos de Oliveira FM, et al. (2015) Assembly of Slx4 signaling complexes behind DNA replication forks. EMBO J.
55. Coulon S, Gaillard PH, Chahwan C, McDonald WH, Yates JR 3rd, et al. (2004) Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast. Mol Biol Cell 15: 71–80. 14528010
56. Coulon S, Noguchi E, Noguchi C, Du LL, Nakamura TM, et al. (2006) Rad22Rad52-dependent repair of ribosomal DNA repeats cleaved by Slx1-Slx4 endonuclease. Mol Biol Cell 17: 2081–2090. 16467377
57. Yan W, Shao Z, Li F, Niu L, Shi Y, et al. (2011) Structural basis of gammaH2AX recognition by human PTIP BRCT5-BRCT6 domains in the DNA damage response pathway. FEBS Lett 585: 3874–3879. doi: 10.1016/j.febslet.2011.10.045 22064073
58. Wang J, Aroumougame A, Lobrich M, Li Y, Chen D, et al. (2014) PTIP associates with Artemis to dictate DNA repair pathway choice. Genes Dev 28: 2693–2698. doi: 10.1101/gad.252478.114 25512557
59. Callen E, Di Virgilio M, Kruhlak MJ, Nieto-Soler M, Wong N, et al. (2013) 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153: 1266–1280. doi: 10.1016/j.cell.2013.05.023 23727112
60. Zimmermann M, de Lange T (2014) 53BP1: pro choice in DNA repair. Trends Cell Biol 24: 108–117. doi: 10.1016/j.tcb.2013.09.003 24094932
61. Forsburg SL, Rhind N (2006) Basic methods for fission yeast. Yeast 23: 173–183. 16498704
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