High-Resolution Mapping of Spontaneous Mitotic Recombination Hotspots on the 1.1 Mb Arm of Yeast Chromosome IV

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Although homologous recombination is an important pathway for the repair of double-stranded DNA breaks in mitotically dividing eukaryotic cells, these events can also have negative consequences, such as loss of heterozygosity (LOH) of deleterious mutations. We mapped about 140 spontaneous reciprocal crossovers on the right arm of the yeast chromosome IV using single-nucleotide-polymorphism (SNP) microarrays. Our mapping and subsequent experiments demonstrate that inverted repeats of Ty retrotransposable elements are mitotic recombination hotspots. We found that the mitotic recombination maps on the two homologs were substantially different and were unrelated to meiotic recombination maps. Additionally, about 70% of the DNA lesions that result in LOH are likely generated during G1 of the cell cycle and repaired during S or G2. We also show that different genetic elements are associated with reciprocal crossover conversion tracts depending on the cell cycle timing of the initiating DSB.

Vyšlo v časopise: High-Resolution Mapping of Spontaneous Mitotic Recombination Hotspots on the 1.1 Mb Arm of Yeast Chromosome IV. PLoS Genet 9(4): e32767. doi:10.1371/journal.pgen.1003434
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003434

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Zdroje

1. AguileraA (2002) The connection between transcription and genomic instability. EMBO J 21: 195–201.

2. GordeninDA, ResnickMA (1998) Yeast ARMs (DNA at-risk motifs) can reveal sources of genome instability. Mutat Res 400: 45–58.

3. VoineaguI, NarayananV, LobachevKS, MirkinSM (2008) Replication stalling at unstable inverted repeats: interplay between DNA hairpins and fork stabilizing proteins. Proc Natl Acad Sci U S A105: 9936–41.

4. GordeninDA, LobachevKS, DegtyarevaNP, MalkovaAL, et al. (1993) Inverted DNA repeats: a source of eukaryotic genomic instability. Mol Cell Biol 13: 5315–22.

5. LobachevKS, GordeninDA, ResnickMA (2002) The Mre11 complex is required for repair of hairpin-capped double-strand breaks and prevention of chromosome rearrangements. Cell 108: 183–93.

6. LemoineFJ, DegtyarevaNP, KokoskaRJ, PetesTD (2008) Reduced levels of DNA polymerase delta induce chromosome fragile site instability in yeast. Mol Cell Biol 28: 5359–68.

7. LemoineFJ, DegtyarevaNP, LobachevK, PetesTD (2005) Chromosomal translocations in yeast induced by low levels of DNA polymerase a model for chromosome fragile sites. Cell 120: 587–98.

8. SymingtonLS, GautierJ (2011) Double-strand break end resection and repair pathway choice. Annu Rev Genet 45: 247–71.

9. ModrichP, LahueR (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem 65: 101–33.

10. Orr-WeaverTL, SzostakJW (1983) Yeast recombination: the association between double-strand gap repair and crossing-over. Proc Natl Acad Sci U S A 80: 4417–21.

11. LeePS, GreenwellPW, DominskaM, GawelM, HamiltonM, 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.

12. LeePS, PetesTD (2010) 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: 7383–8.

13. FachinettiD, BermejoR, CocitoA, MinardiS, KatouY, 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.

14. BarberaMA, PetesTD (2006) Selection and analysis of spontaneous reciprocal mitotic cross-overs in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103: 12819–24.

15. WeiW, McCuskerJ, HymanR, JonesT, NingY, et al. (2007) Genome sequencing and comparative analysis of Saccharomyces cerevisiae strain YJM789. Proc Natl Acad Sci U S A 104: 12825–30.

16. St CharlesJ, Hazkani-CovoE, YinY, AndersenSL, DietrichFS, 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: 1267–84.

17. PaquesF, HaberJE (1999) Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63: 349–404.

18. KimJM, VanguriS, BoekeJD, GabrielA, VoytasDF (1998) Transposable elements and genome organization: a comprehensive survey of retrotransposons revealed by the complete Saccharomyces cerevisiae genome sequence. Genome Res 8: 464–78.

19. MorillonA, BenardL, SpringerM, LesageP (2002) Differential effects of chromatin and Gcn4 on the 50-fold range of expression among individual yeast Ty1 retrotransposons. Mol Cell Biol 22: 2078–88.

20. AzvolinskyA, GiresiPG, LiebJD, ZakianVA (2009) Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Mol Cell 34: 722–34.

21. CapraJA, PaeschkeK, SinghM, ZakianVA (2010) G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae. PLoS Comput Biol 6: e1000861 doi:10.1371/journal.pcbi.1000861.

22. PaeschkeK, CapraJA, ZakianVA (2011) DNA replication through G-quadruplex motifs is promoted by the Saccharomyces cerevisiae Pif1 DNA helicase. Cell 145: 678–91.

23. SternC (1936) Somatic Crossing over and Segregation in Drosophila Melanogaster. Genetics 21: 625–730.

24. HartwellLH, SmithD (1985) Altered fidelity of mitotic chromosome transmission in cell cyle mutants of S. cerevisiae. Genetics 110: 381–395.

25. KleinHL (2001) Spontaneous chromosome loss in Saccharomyces cerevisiae is suppressed by DNA damage checkpoint functions. Genetics 159: 1501–1509.

26. MaloneyDH, FogelS (1980) Mitotic recombination in yeast: isolation and characterization of mutants with enhanced spontaneous mitotic gene conversion rates. Genetics 94: 825–839.

27. GolinJE, EspositoMS (1984) Coincident gene conversion during mitosis in Saccharomyces. Genetics 107: 355–365.

28. SteeleDF, MorrisME, Jinks-RobertsonS (1991) Allelic and ectopic interactions in recombination-defective yeast strains. Genetics 127: 53–60.

29. TangW, DominskaM, GreenwellPW, HarvanekZ, LobachevKS, et al. (2011) Friedreich's ataxia (GAA)n*(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae. PLoS Genet 7: e1001270 doi:10.1371/journal.pgen.1001270.

30. BlitzblauHG, BellGW, RodriguezJ, BellSP, HochwagenA (2007) Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres. Curr Biol 17: 2003–12.

31. BordeV, LinW, NovikovE, PetriniJH, LichtenM, et al. (2004) Association of Mre11p with double-strand break sites during yeast meiosis. Mol Cell 13: 389–401.

32. BuhlerC, BordeV, LichtenM (2007) Mapping meiotic single-strand DNA reveals a new landscape of DNA double-strand breaks in Saccharomyces cerevisiae. PLoS Biol 5: e324 doi:10.1371/journal.pbio.0050324.

33. GertonJL, DeRisiJ, ShroffR, LichtenM, BrownPO, et al. (2000) Global mapping of meiotic recombination hotspots and coldspots in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 97: 11383–90.

34. PanJ, SasakiM, KniewelR, MurakamiH, BlitzblauHG, et al. (2011) A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation. Cell 144: 719–31.

35. PetesTD (2001) Meiotic recombination hot spots and cold spots. Nat Rev Genet 2: 360–9.

36. LobachevKS, ShorBM, TranHT, TaylorW, KeenJD, et al. (1998) Factors affecting inverted repeat stimulation of recombination and deletion in Saccharomyces cerevisiae. Genetics 148: 1507–24.

37. AllersT, LeachDR (1995) DNA palindromes adopt a methylation-resistant conformation that is consistent with DNA cruciform or hairpin formation in vivo. J Mol Biol 252: 70–85.

38. KogoH, InagakiH, OhyeT, KatoT, EmanuelBS, et al. (2007) Cruciform extrusion propensity of human translocation-mediating palindromic AT-rich repeats. Nucleic Acids Res 35: 1198–208.

39. SindenRR, ZhengGX, BrankampRG, AllenKN (1991) On the deletion of inverted repeated DNA in Escherichia coli: effects of length, thermal stability, and cruciform formation in vivo. Genetics 129: 991–1005.

40. LobachevKS, StengerJE, KozyrevaOG, JurkaJ, GordeninDA, et al. (2000) Inverted Alu repeats unstable in yeast are excluded from the human genome. EMBO J 19: 3822–3830.

41. WangJC (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3: 430–40.

42. BranzeiD, FoianiM (2010) Maintaining genome stability at the replication fork. Nat Rev Mol Cell Bio 11: 208–19.

43. BermejoR, DoksaniY, CapraT, KatouYM, TanakaH, et al. (2007) Top1- and Top2-mediated topological transitions at replication forks ensure fork progression and stability and prevent DNA damage checkpoint activation. Gene Dev 21: 1921–36.

44. DiNardoS, VoelkelK, SternglanzR (1984) DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci U S A 81: 2616–20.

45. ManceraE, BourgonR, BrozziA, HuberW, SteinmetzLM (2008) High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454: 479–85.

46. Fishman-LobellJ, HaberJE (1992) Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science 258: 480–4.

47. IvanovEL, HaberJE (1992) RAD1 and RAD10, but not other excision repair genes, are required for double-strand break-induced recombination in Saccharomyces cerevisiae. Mol Cell Biol 15: 2245–51.

48. InbarO, KupiecM (1999) Homology search and choice of homologous partner during mitotic recombination. Mol Cell Biol 19: 4134–42.

49. PaquesF, HaberJE (1997) Two pathways for removal of nonhomologous DNA ends during double-strand break repair in Saccharomyces cerevisiae. Mol Cel Biol 17: 6765–71.

50. SaparbaevM, PrakashL, PrakashS (1996) Requirement of mismatch repair genes MSH2 and MSH3 in the RAD1-RAD10 pathway of mitotic recombination in Saccharomyces cerevisiae. Genetics 142: 727–36.

51. SugawaraN, PâquesF, ColaiacovoM, HaberJE (1997) Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-strand break-induced recombination. P Natl Acad Sci USA 94: 9214–9.

52. LisbyM, RothsteinR, MortensenUH (2001) Rad52 forms DNA repair and recombination centers during S phase. Proc Natl Acad Sci U S A 98: 8276–82.

53. AylonY, LiefshitzB, KupiecM (2004) The CDK regulates repair of double-strand breaks by homologous recombination during the cell cycle. EMBO J 23: 4868–75.

54. IraG, PellicioliA, BalijjaA, WangX, FioraniS (2004) DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature 431: 1011–7.

55. CovoS, WestmorelandJW, GordeninDA, ResnickMA (2010) Cohesin is limiting for the suppression of DNA damage-induced recombination between homologous chromosomes. PLoS Genet 7: e1001006 doi:10.1371/journal.pgen.1001006.

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

57. Guthrie C, Fink GR (1991) Guide to yeast genetics and molecular biology. San Diego: Academic Press.

58. Altman DG (1991) Practical statistics for medical research. London: Chapman & Hall.

59. HochbergY, BenjaminiY (1990) More powerful procedures for multiple significance testing. Stat Med 9: 811–8.