Histone H3K56 Acetylation, Rad52, and Non-DNA Repair Factors Control Double-Strand Break Repair Choice with the Sister Chromatid

English version České info

DNA double-strand breaks (DSBs) are harmful lesions that arise mainly during replication. The choice of the sister chromatid as the preferential repair template is critical for genome integrity, but the mechanisms that guarantee this choice are unknown. Here we identify new genes with a specific role in assuring the sister chromatid as the preferred repair template. Physical analyses of sister chromatid recombination (SCR) in 28 selected mutants that increase Rad52 foci and inter-homolog recombination uncovered 8 new genes required for SCR. These include the SUMO/Ub-SUMO protease Wss1, the stress-response proteins Bud27 and Pdr10, the ADA histone acetyl-transferase complex proteins Ahc1 and Ada2, as well as the Hst3 and Hst4 histone deacetylase and the Rtt109 histone acetyl-transferase genes, whose target is histone H3 Lysine 56 (H3K56). Importantly, we use mutations in H3K56 residue to A, R, and Q to reveal that H3K56 acetylation/deacetylation is critical to promote SCR as the major repair mechanism for replication-born DSBs. The same phenotype is observed for a particular class of rad52 alleles, represented by rad52-C180A, with a DSB repair defect but a spontaneous hyper-recombination phenotype. We propose that specific Rad52 residues, as well as the histone H3 acetylation/deacetylation state of chromatin and other specific factors, play an important role in identifying the sister as the choice template for the repair of replication-born DSBs. Our work demonstrates the existence of specific functions to guarantee SCR as the main repair event for replication-born DSBs that can occur by two pathways, one Rad51-dependent and the other Pol32-dependent. A dysfunction can lead to genome instability as manifested by high levels of homolog recombination and DSB accumulation.

Vyšlo v časopise: Histone H3K56 Acetylation, Rad52, and Non-DNA Repair Factors Control Double-Strand Break Repair Choice with the Sister Chromatid. PLoS Genet 9(1): e32767. doi:10.1371/journal.pgen.1003237
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003237

Souhrn

Zdroje

1. KadykLC, HartwellLH (1992) Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics 132 : 387–402.

2. JohnsonRD, JasinM (2000) Sister chromatid gene conversion is a prominent double-strand break repair pathway in mammalian cells. EMBO J 19 : 3398–3407.

3. Gonzalez-BarreraS, Cortes-LedesmaF, WellingerRE, AguileraA (2003) Equal sister chromatid exchange is a major mechanism of double-strand break repair in yeast. Mol Cell 11 : 1661–1671.

4. Cortes-LedesmaF, AguileraA (2006) Double-strand breaks arising by replication through a nick are repaired by cohesin-dependent sister-chromatid exchange. EMBO Rep 7 : 919–926.

5. GunjanA, PaikJ, VerreaultA (2005) Regulation of histone synthesis and nucleosome assembly. Biochimie 87 : 625–635.

6. MasumotoH, HawkeD, KobayashiR, VerreaultA (2005) A role for cell-cycle-regulated histone H3 lysine 56 acetylation in the DNA damage response. Nature 436 : 294–298.

7. MaasNL, MillerKM, DeFazioLG, ToczyskiDP (2006) Cell cycle and checkpoint regulation of histone H3 K56 acetylation by Hst3 and Hst4. Mol Cell 23 : 109–119.

8. ChenCC, CarsonJJ, FeserJ, TamburiniB, ZabaronickS, et al. (2008) Acetylated lysine 56 on histone H3 drives chromatin assembly after repair and signals for the completion of repair. Cell 134 : 231–243.

9. DasC, LuciaMS, HansenKC, TylerJK (2009) CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459 : 113–117.

10. TjeertesJV, MillerKM, JacksonSP (2009) Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28 : 1878–1889.

11. YuanJ, PuM, ZhangZ, LouZ (2009) Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8 : 1747–1753.

12. OzdemirA, SpicugliaS, LasonderE, VermeulenM, CampsteijnC, et al. (2005) Characterization of lysine 56 of histone H3 as an acetylation site in Saccharomyces cerevisiae. J Biol Chem 280 : 25949–25952.

13. AlvaroD, LisbyM, RothsteinR (2007) Genome-wide analysis of Rad52 foci reveals diverse mechanisms impacting recombination. PLoS Genet 3: e228 doi:10.1371/journal.pgen.0030228.

14. MaloneRE, MonteloneBA, EdwardsC, CarneyK, HoekstraMF (1988) A reexamination of the role of the RAD52 gene in spontaneous mitotic recombination. Curr Genet 14 : 211–223.

15. LettierG, FengQ, de MayoloAA, ErdenizN, ReidRJ, et al. (2006) The role of DNA double-strand breaks in spontaneous homologous recombination in S. cerevisiae. PLoS Genet 2: e194 doi:10.1371/journal.pgen.0030194.

16. MullenJR, ChenCF, BrillSJ (2010) Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase. Mol Cell Biol 30 : 3737–3748.

17. EberharterA, SternerDE, SchieltzD, HassanA, YatesJR3rd, et al. (1999) The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. Mol Cell Biol 19 : 6621–6631.

18. Cortes-LedesmaF, TousC, AguileraA (2007) Different genetic requirements for repair of replication-born double-strand breaks by sister-chromatid recombination and break-induced replication. Nucleic Acids Res 35 : 6560–6570.

19. DeplazesA, MockliN, LukeB, AuerbachD, PeterM (2009) Yeast Uri1p promotes translation initiation and may provide a link to cotranslational quality control. EMBO J 28 : 1429–1441.

20. RockwellNC, WolfgerH, KuchlerK, ThornerJ (2009) ABC transporter Pdr10 regulates the membrane microenvironment of Pdr12 in Saccharomyces cerevisiae. J Membr Biol 229 : 27–52.

21. HoriuchiJ, SilvermanN, MarcusGA, GuarenteL (1995) ADA3, a putative transcriptional adaptor, consists of two separable domains and interacts with ADA2 and GCN5 in a trimeric complex. Mol Cell Biol 15 : 1203–1209.

22. XuF, ZhangK, GrunsteinM (2005) Acetylation in histone H3 globular domain regulates gene expression in yeast. Cell 121 : 375–385.

23. FasulloMT, DavisRW (1987) Recombinational substrates designed to study recombination between unique and repetitive sequences in vivo. Proc Natl Acad Sci U S A 84 : 6215–6219.

24. CelicI, VerreaultA, BoekeJD (2008) Histone H3 K56 hyperacetylation perturbs replisomes and causes DNA damage. Genetics 179 : 1769–1784.

25. Moriel-CarreteroM, AguileraA (2010a) A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51 -⁠ or Pol32-mediated restart mechanisms. Mol Cell 37 : 690–701.

26. LydeardJR, JainS, YamaguchiM, HaberJE (2007) Break-induced replication and telomerase-independent telomere maintenance require Pol32. Nature 448 : 820–823.

27. Torres-RosellJ, SunjevaricI, De PiccoliG, SacherM, Eckert-BouletN, et al. (2007) The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Nat Cell Biol 9 : 923–931.

28. PalancadeB, DoyeV (2008) Sumoylating and desumoylating enzymes at nuclear pores: underpinning their unexpected duties? Trends Cell Biol 18 : 174–183.

29. GalantyY, BelotserkovskayaR, CoatesJ, PoloS, MillerKM, et al. (2009) Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 462 : 935–939.

30. KalocsayM, HillerNJ, JentschS (2009) Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell 33 : 335–343.

31. De PiccoliG, Cortes-LedesmaF, IraG, Torres-RosellJ, UhleS, et al. (2006) Smc5-Smc6 mediate DNA double-strand-break repair by promoting sister-chromatid recombination. Nat Cell Biol 8 : 1032–1034.

32. PottsPR, PorteusMH, YuH (2006) Human SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaks. EMBO J 25 : 3377–3388.

33. SacherM, PfanderB, HoegeC, JentschS (2006) Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol 8 : 1284–1290.

34. AltmannovaV, Eckert-BouletN, ArnericM, KolesarP, ChaloupkovaR, et al. Rad52 SUMOylation affects the efficiency of the DNA repair. Nucleic Acids Res 38 : 4708–4721.

35. SuganumaT, WorkmanJL Signals and combinatorial functions of histone modifications. Annu Rev Biochem 80 : 473–499.

36. RechtJ, TsubotaT, TannyJC, DiazRL, BergerJM, et al. (2006) Histone chaperone Asf1 is required for histone H3 lysine 56 acetylation, a modification associated with S phase in mitosis and meiosis. Proc Natl Acad Sci U S A 103 : 6988–6993.

37. GarciaBA, HakeSB, DiazRL, KauerM, MorrisSA, et al. (2007) Organismal differences in post-translational modifications in histones H3 and H4. J Biol Chem 282 : 7641–7655.

38. WurteleH, KaiserGS, BacalJ, St-HilaireE, LeeEH, et al. (2012) Histone H3 lysine 56 acetylation and the response to DNA replication fork damage. Mol Cell Biol 32 : 154–72.

39. AguileraA, Gomez-GonzalezB (2008) Genome instability: a mechanistic view of its causes and consequences. Nat Rev Genet 9 : 204–217.

40. PradoF, Cortes-LedesmaF, AguileraA (2004) The absence of the yeast chromatin assembly factor Asf1 increases genomic instability and sister chromatid exchange. EMBO Rep 5 : 497–502.

41. EmiliA, SchieltzDM, YatesJR3rd, HartwellLH (2001) Dynamic interaction of DNA damage checkpoint protein Rad53 with chromatin assembly factor Asf1. Mol Cell 7 : 13–20.

42. DriscollR, HudsonA, JacksonSP (2007) Yeast Rtt109 promotes genome stability by acetylating histone H3 on lysine 56. Science 315 : 649–652.

43. YangB, MillerA, KirchmaierAL (2008) HST3/HST4-dependent deacetylation of lysine 56 of histone H3 in silent chromatin. Mol Biol Cell 19 : 4993–5005.

44. de MayoloAA, SunjevaricI, ReidR, MortensenUH, RothsteinR, et al. The rad52-Y66A allele alters the choice of donor template during spontaneous chromosomal recombination. DNA Repair (Amst) 9 : 23–32.

45. Moriel-CarreteroM, AguileraA (2010b) Replication fork breakage and re-start: New insights into Rad3/XPD-associated deficiencies. Cell Cycle 9 : 2958–2962.

46. Gonzalez-BarreraS, Garcia-RubioM, AguileraA (2002) Transcription and double-strand breaks induce similar mitotic recombination events in Saccharomyces cerevisiae. Genetics 162 : 603–614.

47. LisbyM, RothsteinR, MortensenUH (2001) Rad52 forms DNA repair and recombination centers during S phase. Proc Natl Acad Sci U S A 98 : 8276–8282.

48. Garcia-RubioM, HuertasP, Gonzalez-BarreraS, AguileraA (2003) Recombinogenic effects of DNA-damaging agents are synergistically increased by transcription in Saccharomyces cerevisiae. New insights into transcription-associated recombination. Genetics 165 : 457–466.

49. LisbyM, MortensenUH, RothsteinR (2003) Colocalization of multiple DNA double-strand breaks at a single Rad52 repair centre. Nat Cell Biol 5 : 572–577.