Recombination between Homologous Chromosomes Induced by Unrepaired UV-Generated DNA Damage Requires Mus81p and Is Suppressed by Mms2p

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Ultraviolet (UV) light is a ubiquitous agent of exogenous DNA damage. In normal cells, the nucleotide excision repair (NER) pathway is the primary mechanism for repair of UV-induced DNA lesions. Defects in the NER pathway are associated with the human disease xeroderma pigmentosum (XP), and XP patients are prone to skin cancer. Mitotic recombination is strongly stimulated by UV treatment. In this study, we examined whether such stimulation requires the NER pathway. We show that, in the absence of NER, UV is still able to greatly induce recombination. We then characterized a nuclease that is required to generate recombinogenic breaks. Finally, we examined a previously known recombinogenic pathway called the “post-replication repair (PRR) pathway.” Our results suggest that the PRR pathway mainly promotes recombination between sister chromatids, and suppresses recombination between chromosome homologs.

Vyšlo v časopise: Recombination between Homologous Chromosomes Induced by Unrepaired UV-Generated DNA Damage Requires Mus81p and Is Suppressed by Mms2p. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005026
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005026

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Zdroje

1. Friedberg EC, Walker GC, Wolfram S, Wood RD, Schultz RA, et al. (2006) DNA repair and mutagenesis; Friedberg EC, editor. Washington, D.C.: ASM Press.

2. Galli A, Schiestl RH (1999) Cell division transforms mutagenic lesions into deletion-recombinagenic lesions in yeast cells. Mutat Res 429: 13–26. 10434021

3. St Charles J, Hazkani-Covo E, Yin Y, Andersen SL, Dietrich FS, et al. (2012) High-resolution genome-wide analysis of irradiated (UV and gamma-rays) diploid yeast cells reveals a high frequency of genomic loss of heterozygosity (LOH) events. Genetics 190: 1267–1284. doi: 10.1534/genetics.111.137927 22267500

4. Yin Y, Petes TD (2013) Genome-wide high-resolution mapping of UV-induced mitotic recombination events in Saccharomyces cerevisiae. PLoS Genet 9: e1003894. doi: 10.1371/journal.pgen.1003894 24204306

5. Nakai S, Mortimer RK (1969) Studies on the genetic mechanism of radiation-induced mitotic segregation in yeast. Mol Gen Genet 103: 329–338. 5803902

6. Kadyk LC, Hartwell LH (1993) Replication-dependent sister chromatid recombination in rad1 mutants of Saccharomyces cerevisiae. Genetics 133: 469–487. 8454200

7. Mazon G, Lam AF, Ho CK, Kupiec M, Symington LS (2012) The Rad1-Rad10 nuclease promotes chromosome translocations between dispersed repeats. Nat Struct Mol Biol 19: 964–971. doi: 10.1038/nsmb.2359 22885325

8. Schwartz EK, Heyer WD (2011) Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes. Chromosoma 120: 109–127. doi: 10.1007/s00412-010-0304-7 21369956

9. Guzder SN, Sung P, Prakash L, Prakash S (1993) Yeast DNA-repair gene RAD14 encodes a zinc metalloprotein with affinity for ultraviolet-damaged DNA. Proc Natl Acad Sci U S A 90: 5433–5437. 8516285

10. Courcelle J, Hanawalt PC (2003) RecA-dependent recovery of arrested DNA replication forks. Annu Rev Genet 37: 611–646. 14616075

11. Lopes M, Foiani M, Sogo JM (2006) Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell 21: 15–27. 16387650

12. Mitchel K, Zhang H, Welz-Voegele C, Jinks-Robertson S (2010) Molecular structures of crossover and noncrossover intermediates during gap repair in yeast: implications for recombination. Mol Cell 38: 211–222. doi: 10.1016/j.molcel.2010.02.028 20417600

13. Donnianni RA, Symington LS (2013) Break-induced replication occurs by conservative DNA synthesis. Proc Natl Acad Sci U S A 110: 13475–13480. doi: 10.1073/pnas.1309800110 23898170

14. Saini N, Ramakrishnan S, Elango R, Ayyar S, Zhang Y, et al. (2013) Migrating bubble during break-induced replication drives conservative DNA synthesis. Nature 502: 389–392. doi: 10.1038/nature12584 24025772

15. Ho CK, Mazon G, Lam AF, Symington LS (2010) Mus81 and Yen1 promote reciprocal exchange during mitotic recombination to maintain genome integrity in budding yeast. Mol Cell 40: 988–1000. doi: 10.1016/j.molcel.2010.11.016 21172663

16. Snow R (1968) Recombination in ultraviolet-sensitive strains of Saccharomyces cerevisiae. Mutat Res 6: 409–418. 5728832

17. Sekelsky JJ, McKim KS, Chin GM, Hawley RS (1995) The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics 141: 619–627. 8647398

18. Boiteux S, Jinks-Robertson S (2013) DNA repair mechanisms and the bypass of DNA damage in Saccharomyces cerevisiae. Genetics 193: 1025–1064. doi: 10.1534/genetics.112.145219 23547164

19. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419: 135–141. 12226657

20. St Charles J, Petes TD (2013) High-resolution mapping of spontaneous mitotic recombination hotspots on the 1.1 Mb arm of yeast chromosome IV. PLoS Genet 9: e1003434. doi: 10.1371/journal.pgen.1003434 23593029

21. Lee PS, Greenwell PW, Dominska M, Gawel M, Hamilton M, et al. (2009) A fine-structure map of spontaneous mitotic crossovers in the yeast Saccharomyces cerevisiae. PLoS Genet 5: e1000410. doi: 10.1371/journal.pgen.1000410 19282969

22. Lee PS, Petes TD (2010) From the Cover: mitotic gene conversion events induced in G1-synchronized yeast cells by gamma rays are similar to spontaneous conversion events. Proc Natl Acad Sci U S A 107: 7383–7388. doi: 10.1073/pnas.1001940107 20231456

23. Chua P, Jinks-Robertson S (1991) Segregation of recombinant chromatids following mitotic crossing over in yeast. Genetics 129: 359–369. 1660426

24. Barbera MA, Petes TD (2006) Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103: 12819–12824. 16908833

25. Fachinetti D, Bermejo R, Cocito A, Minardi S, Katou Y, et al. (2010) Replication termination at eukaryotic chromosomes is mediated by Top2 and occurs at genomic loci containing pausing elements. Mol Cell 39: 595–605. doi: 10.1016/j.molcel.2010.07.024 20797631

26. 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

27. Interthal H, Heyer WD (2000) MUS81 encodes a novel helix-hairpin-helix protein involved in the response to UV- and methylation-induced DNA damage in Saccharomyces cerevisiae. Mol Gen Genet 263: 812–827. 10905349

28. Song W, Dominska M, Greenwell PW, Petes TD (2014) Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A.

29. Fishman-Lobell J, Haber JE (1992) Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258: 480–484. 1411547

30. McCulley JL, Petes TD (2010) Chromosome rearrangements and aneuploidy in yeast strains lacking both Tel1p and Mec1p reflect deficiencies in two different mechanisms. Proc Natl Acad Sci U S A 107: 11465–11470. doi: 10.1073/pnas.1006281107 20534547

31. Lam LH, Reynolds RJ (1987) DNA sequence dependence of closely opposed cyclobutyl pyrimidine dimers induced by UV radiation. Mutat Res 178: 167–176. 3587252

32. Covo S, Ma W, Westmoreland JW, Gordenin DA, Resnick MA (2012) Understanding the origins of UV-induced recombination through manipulation of sister chromatid cohesion. Cell Cycle 11: 3937–3944. doi: 10.4161/cc.21945 22987150

33. Yin Y, Petes TD (2014) The Role of Exo1p Exonuclease in DNA End-Resection To Generate Gene Conversion Tracts in Saccharomyces cerevisiae. Genetics.

34. Ma W, Westmoreland JW, Resnick MA (2013) Homologous recombination rescues ssDNA gaps generated by nucleotide excision repair and reduced translesion DNA synthesis in yeast G2 cells. Proc Natl Acad Sci U S A 110: E2895–2904. doi: 10.1073/pnas.1301676110 23858457

35. Ying S, Minocherhomji S, Chan KL, Palmai-Pallag T, Chu WK, et al. (2013) MUS81 promotes common fragile site expression. Nat Cell Biol 15: 1001–1007. doi: 10.1038/ncb2773 23811685

36. Regairaz M, Zhang YW, Fu H, Agama KK, Tata N, et al. (2011) Mus81-mediated DNA cleavage resolves replication forks stalled by topoisomerase I-DNA complexes. J Cell Biol 195: 739–749. doi: 10.1083/jcb.201104003 22123861

37. Andersen SL, Kuo HK, Savukoski D, Brodsky MH, Sekelsky J (2011) Three structure-selective endonucleases are essential in the absence of BLM helicase in Drosophila. PLoS Genet 7: e1002315. doi: 10.1371/journal.pgen.1002315 22022278

38. Ashton TM, Mankouri HW, Heidenblut A, McHugh PJ, Hickson ID (2011) Pathways for Holliday junction processing during homologous recombination in Saccharomyces cerevisiae. Mol Cell Biol 31: 1921–1933. doi: 10.1128/MCB.01130-10 21343337

39. Munoz-Galvan S, Tous C, Blanco MG, Schwartz EK, Ehmsen KT, et al. (2012) Distinct roles of Mus81, Yen1, Slx1-Slx4, and Rad1 nucleases in the repair of replication-born double-strand breaks by sister chromatid exchange. Mol Cell Biol 32: 1592–1603. doi: 10.1128/MCB.00111-12 22354996

40. Blanco MG, Matos J, West SC (2014) Dual control of Yen1 nuclease activity and cellular localization by Cdk and Cdc14 prevents genome instability. Mol Cell 54: 94–106. doi: 10.1016/j.molcel.2014.02.011 24631285

41. Katz SS, Gimble FS, Storici F (2014) To nick or not to nick: comparison of I-SceI single- and double-strand break-induced recombination in yeast and human cells. PLoS One 9: e88840. doi: 10.1371/journal.pone.0088840 24558436

42. Giannattasio M, Zwicky K, Follonier C, Foiani M, Lopes M, et al. (2014) Visualization of recombination-mediated damage bypass by template switching. Nat Struct Mol Biol 21: 884–892. doi: 10.1038/nsmb.2888 25195051

43. Daigaku Y, Davies AA, Ulrich HD (2010) Ubiquitin-dependent DNA damage bypass is separable from genome replication. Nature 465: 951–955. doi: 10.1038/nature09097 20453836

44. Torres-Ramos CA, Prakash S, Prakash L (2002) Requirement of RAD5 and MMS2 for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Mol Cell Biol 22: 2419–2426. 11884624

45. Thomas BJ, Rothstein R (1989) Elevated recombination rates in transcriptionally active DNA. Cell 56: 619–630. 2645056

46. Wei W, McCusker JH, Hyman RW, Jones T, Ning Y, et al. (2007) Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. Proc Natl Acad Sci U S A 104: 12825–12830. 17652520

47. Guthrie C, Fink GR (2002) Guide to yeast genetics and molecular and cell biology, Part C. Methods in enzymology v 351. Amsterdam; Boston: Academic Press,. pp. 1 online resource (xxxvi, 735 p.

48. Hochberg Y, Benjamini Y (1990) More powerful procedures for multiple significance testing. Stat Med 9: 811–818. 2218183