Combinatorial Regulation of Meiotic Holliday Junction Resolution in by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases

English version České info

Holliday junctions (HJs) are cruciform DNA structures that are created during recombination events. It is a matter of considerable importance to determine the resolvase(s) that promote resolution of these structures. We previously reported that C. elegans GEN-1 is a symmetrically cleaving HJ resolving enzyme required for recombinational repair, but we could not find an overt role in meiotic recombination. Here we identify C. elegans proteins involved in resolving meiotic HJs. We found no evidence for a redundant meiotic function of GEN-1. In contrast, we discovered two redundant HJ resolution pathways likely coordinated by the SLX-4 scaffold protein and also involving the HIM-6/BLM helicase. SLX-4 associates with the SLX-1, MUS-81 and XPF-1 nucleases and has been implicated in meiotic recombination in C. elegans. We found that C. elegans [mus-81; xpf-1], [slx-1; xpf-1], [mus-81; him-6] and [slx-1; him-6] double mutants showed a similar reduction in survival rates as slx-4. Analysis of meiotic diakinesis chromosomes revealed a distinct phenotype in these double mutants. Instead of wild-type bivalent chromosomes, pairs of “univalents” linked by chromatin bridges occur. These linkages depend on the conserved meiosis-specific transesterase SPO-11 and can be restored by ionizing radiation, suggesting that they represent unresolved meiotic HJs. This suggests the existence of two major resolvase activities, one provided by XPF-1 and HIM-6, the other by SLX-1 and MUS-81. In all double mutants crossover (CO) recombination is reduced but not abolished, indicative of further redundancy in meiotic HJ resolution. Real time imaging revealed extensive chromatin bridges during the first meiotic division that appear to be eventually resolved in meiosis II, suggesting back-up resolution activities acting at or after anaphase I. We also show that in HJ resolution mutants, the restructuring of chromosome arms distal and proximal to the CO still occurs, suggesting that CO initiation but not resolution is likely to be required for this process.

Vyšlo v časopise: Combinatorial Regulation of Meiotic Holliday Junction Resolution in by HIM-6 (BLM) Helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 Nucleases. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003591
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003591

Souhrn

Zdroje

1. SunH, TrecoD, SchultesNP, SzostakJW (1989) Double-strand breaks at an initiation site for meiotic gene conversion. Nature 338: 87–90.

2. KeeneyS, GirouxCN, KlecknerN (1997) Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88: 375–384.

3. LuiDY, ColaiacovoMP (2013) Meiotic Development in Caenorhabditis elegans. Adv Exp Med Biol 757: 133–170.

4. 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.

5. MoensPB, KolasNK, TarsounasM, MarconE, CohenPE, et al. (2002) The time course and chromosomal localization of recombination-related proteins at meiosis in the mouse are compatible with models that can resolve the early DNA-DNA interactions without reciprocal recombination. J Cell Sci 115: 1611–1622.

6. RosuS, LibudaDE, VilleneuveAM (2011) Robust crossover assurance and regulated interhomolog access maintain meiotic crossover number. Science 334: 1286–1289.

7. AlpiA, PasierbekP, GartnerA, LoidlJ (2003) Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans. Chromosoma 112: 6–16.

8. ColaiacovoMP, MacQueenAJ, Martinez-PerezE, McDonaldK, AdamoA, et al. (2003) Synaptonemal complex assembly in C. elegans is dispensable for loading strand-exchange proteins but critical for proper completion of recombination. Dev Cell 5: 463–474.

9. FranklinAE, McElverJ, SunjevaricI, RothsteinR, BowenB, et al. (1999) Three-dimensional microscopy of the Rad51 recombination protein during meiotic prophase. Plant Cell 11: 809–824.

10. HillersKJ, VilleneuveAM (2003) Chromosome-wide control of meiotic crossing over in C. elegans. Curr Biol 13: 1641–1647.

11. Martinez-PerezE, ColaiacovoMP (2009) Distribution of meiotic recombination events: talking to your neighbors. Curr Opin Genet Dev 19: 105–112.

12. KroghBO, SymingtonLS (2004) Recombination proteins in yeast. Annu Rev Genet 38: 233–271.

13. ChapmanJR, TaylorMR, BoultonSJ (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell 47: 497–510.

14. De MuytA, JessopL, KolarE, SourirajanA, ChenJ, et al. (2012) BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism. Mol Cell 46: 43–53.

15. BarberLJ, YoudsJL, WardJD, McIlwraithMJ, O'NeilNJ, et al. (2008) RTEL1 maintains genomic stability by suppressing homologous recombination. Cell 135: 261–271.

16. BishopDK, ZicklerD (2004) Early decision; meiotic crossover interference prior to stable strand exchange and synapsis. Cell 117: 9–15.

17. AllersT, LichtenM (2001) Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106: 47–57.

18. BornerGV, KlecknerN, HunterN (2004) Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117: 29–45.

19. ZetkaM, RoseA (1995) The genetics of meiosis in Caenorhabditis elegans. Trends Genet 11: 27–31.

20. YoudsJL, MetsDG, McIlwraithMJ, MartinJS, WardJD, et al. (2010) RTEL-1 enforces meiotic crossover interference and homeostasis. Science 327: 1254–1258.

21. WickyC, AlpiA, PassannanteM, RoseA, GartnerA, et al. (2004) Multiple genetic pathways involving the Caenorhabditis elegans Bloom's syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Mol Cell Biol 24: 5016–5027.

22. HollidayR (1964) A mechanism for gene conversion in fungi. Genet Res 5: 282–304.

23. SzostakJW, Orr-WeaverTL, RothsteinRJ, StahlFW (1983) The double-strand-break repair model for recombination. Cell 33: 25–35.

24. BzymekM, ThayerNH, OhSD, KlecknerN, HunterN (2010) Double Holliday junctions are intermediates of DNA break repair. Nature 464: 937–941.

25. CromieGA, HyppaRW, TaylorAF, ZakharyevichK, HunterN, et al. (2006) Single Holliday junctions are intermediates of meiotic recombination. Cell 127: 1167–1178.

26. SchwachaA, KlecknerN (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83: 783–791.

27. WuL, HicksonID (2003) The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426: 870–874.

28. SvendsenJM, HarperJW (2010) GEN1/Yen1 and the SLX4 complex: Solutions to the problem of Holliday junction resolution. Genes Dev 24: 521–536.

29. SchwartzEK, HeyerWD (2011) Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes. Chromosoma 120: 109–127.

30. WhiteMF, LilleyDM (1997) Characterization of a Holliday junction-resolving enzyme from Schizosaccharomyces pombe. Mol Cell Biol 17: 6465–6471.

31. LilleyDM, WhiteMF (2001) The junction-resolving enzymes. Nat Rev Mol Cell Biol 2: 433–443.

32. BennettRJ, DunderdaleHJ, WestSC (1993) Resolution of Holliday junctions by RuvC resolvase: cleavage specificity and DNA distortion. Cell 74: 1021–1031.

33. WestSC (2009) The search for a human Holliday junction resolvase. Biochem Soc Trans 37: 519–526.

34. IpSC, RassU, BlancoMG, FlynnHR, SkehelJM, et al. (2008) Identification of Holliday junction resolvases from humans and yeast. Nature 456: 357–361.

35. BaillyAP, FreemanA, HallJ, DeclaisAC, AlpiA, et al. (2010) The Caenorhabditis elegans homolog of Gen1/Yen1 resolvases links DNA damage signaling to DNA double-strand break repair. PLoS Genet 6: e1001025.

36. BlancoMG, MatosJ, RassU, IpSC, WestSC (2010) Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae. DNA Repair (Amst) 9: 394–402.

37. AgmonN, YovelM, HarariY, LiefshitzB, KupiecM (2011) The role of Holliday junction resolvases in the repair of spontaneous and induced DNA damage. Nucleic Acids Res 39: 7009–7019.

38. AshtonTM, MankouriHW, HeidenblutA, McHughPJ, HicksonID (2011) Pathways for Holliday junction processing during homologous recombination in Saccharomyces cerevisiae. Mol Cell Biol 31: 1921–1933.

39. BoddyMN, GaillardPH, McDonaldWH, ShanahanP, YatesJR3rd, et al. (2001) Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107: 537–548.

40. MatosJ, BlancoMG, MaslenS, SkehelJM, WestSC (2011) Regulatory control of the resolution of DNA recombination intermediates during meiosis and mitosis. Cell 147: 158–172.

41. HollowayJK, BoothJ, EdelmannW, McGowanCH, CohenPE (2008) MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS Genet 4: e1000186.

42. SaitoTT, YoudsJL, BoultonSJ, ColaiacovoMP (2009) Caenorhabditis elegans HIM-18/SLX-4 interacts with SLX-1 and XPF-1 and maintains genomic integrity in the germline by processing recombination intermediates. PLoS Genet 5: e1000735.

43. AndersenSL, BergstralhDT, KohlKP, LaRocqueJR, MooreCB, et al. (2009) Drosophila MUS312 and the vertebrate ortholog BTBD12 interact with DNA structure-specific endonucleases in DNA repair and recombination. Mol Cell 35: 128–135.

44. FekairiS, ScaglioneS, ChahwanC, TaylorER, TissierA, et al. (2009) Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138: 78–89.

45. MunozIM, HainK, DeclaisAC, GardinerM, TohGW, et al. (2009) Coordination of structure-specific nucleases by human SLX4/BTBD12 is required for DNA repair. Mol Cell 35: 116–127.

46. SvendsenJM, SmogorzewskaA, SowaME, O'ConnellBC, GygiSP, et al. (2009) Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair. Cell 138: 63–77.

47. SaitoTT, MohideenF, MeyerK, HarperJW, ColaiacovoMP (2012) SLX-1 Is Required for Maintaining Genomic Integrity and Promoting Meiotic Noncrossovers in the Caenorhabditis elegans Germline. PLoS Genet 8: e1002888.

48. SaitoTT, LuiDY, KimH-M, MeyerK, ColaiacovoMP (2013) Interplay between structure-specific endonucleases for crossover control during Caenorhabditis elegans meiosis. PLoS Genet in press

49. CicciaA, McDonaldN, WestSC (2008) Structural and functional relationships of the XPF/MUS81 family of proteins. Annu Rev Biochem 77: 259–287.

50. Al-MinawiAZ, Saleh-GohariN, HelledayT (2008) The ERCC1/XPF endonuclease is required for efficient single-strand annealing and gene conversion in mammalian cells. Nucleic Acids Res 36: 1–9.

51. 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: 480–484.

52. SekelskyJJ, McKimKS, ChinGM, HawleyRS (1995) The Drosophila meiotic recombination gene mei-9 encodes a homologue of the yeast excision repair protein Rad1. Genetics 141: 619–627.

53. ZakharyevichK, MaY, TangS, HwangPY, BoiteuxS, et al. (2010) Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Mol Cell 40: 1001–1015.

54. ZakharyevichK, TangS, MaY, HunterN (2012) Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. Cell 149: 334–347.

55. ScharerOD, CampbellAJ (2009) Wedging out DNA damage. Nat Struct Mol Biol 16: 102–104.

56. GoodyerW, KaitnaS, CouteauF, WardJD, BoultonSJ, et al. (2008) HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. Dev Cell 14: 263–274.

57. MacQueenAJ, ColaiacovoMP, McDonaldK, VilleneuveAM (2002) Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. Genes Dev 16: 2428–2442.

58. La VolpeA, BarchiM (2012) Meiotic double strand breaks repair in sexually reproducing eukaryotes: we are not all equal. Exp Cell Res 318: 1333–1339.

59. DernburgAF, McDonaldK, MoulderG, BarsteadR, DresserM, et al. (1998) Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell 94: 387–398.

60. WechslerT, NewmanS, WestSC (2011) Aberrant chromosome morphology in human cells defective for Holliday junction resolution. Nature 471: 642–646.

61. YokooR, ZawadzkiKA, NabeshimaK, DrakeM, ArurS, et al. (2012) COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers. Cell 149: 75–87.

62. MetsDG, MeyerBJ (2009) Condensins regulate meiotic DNA break distribution, thus crossover frequency, by controlling chromosome structure. Cell 139: 73–86.

63. AdamoA, MontemauriP, SilvaN, WardJD, BoultonSJ, et al. (2008) BRC-1 acts in the inter-sister pathway of meiotic double-strand break repair. EMBO Rep 9: 287–292.

64. BickelJS, ChenL, HaywardJ, YeapSL, AlkersAE, et al. (2010) Structural maintenance of chromosomes (SMC) proteins promote homolog-independent recombination repair in meiosis crucial for germ cell genomic stability. PLoS Genet 6: e1001028.

65. HillersKJ, VilleneuveAM (2009) Analysis of meiotic recombination in Caenorhabditis elegans. Methods Mol Biol 557: 77–97.

66. LimJG, StineRR, YanowitzJL (2008) Domain-specific regulation of recombination in Caenorhabditis elegans in response to temperature, age and sex. Genetics 180: 715–726.

67. BhallaN, WynneDJ, JantschV, DernburgAF (2008) ZHP-3 acts at crossovers to couple meiotic recombination with synaptonemal complex disassembly and bivalent formation in C. elegans. PLoS Genet 4: e1000235.

68. JantschV, PasierbekP, MuellerMM, SchweizerD, JantschM, et al. (2004) Targeted gene knockout reveals a role in meiotic recombination for ZHP-3, a Zip3-related protein in Caenorhabditis elegans. Mol Cell Biol 24: 7998–8006.

69. NabeshimaK, VilleneuveAM, ColaiacovoMP (2005) Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC. J Cell Biol 168: 683–689.

70. Martinez-PerezE, SchvarzsteinM, BarrosoC, LightfootJ, DernburgAF, et al. (2008) Crossovers trigger a remodeling of meiotic chromosome axis composition that is linked to two-step loss of sister chromatid cohesion. Genes Dev 22: 2886–2901.

71. SchvarzsteinM, WignallSM, VilleneuveAM (2010) Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes. Genes Dev 24: 219–228.

72. Martinez-PerezE, VilleneuveAM (2005) HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis. Genes Dev 19: 2727–2743.

73. O'NeilNJ, MartinJS, YoudsJL, WardJD, PetalcorinMIR, et al. (2013) Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during C. elegans meiosis. PLoS Genet in press

74. RassU, ComptonSA, MatosJ, SingletonMR, IpSC, et al. (2010) Mechanism of Holliday junction resolution by the human GEN1 protein. Genes Dev 24: 1559–1569.

75. WestSC (1995) Holliday junctions cleaved by Rad1? Nature 373: 27–28.

76. HabrakenY, SungP, PrakashL, PrakashS (1994) Holliday junction cleavage by yeast Rad1 protein. Nature 371: 531–534.

77. AndersenSL, KuoHK, SavukoskiD, BrodskyMH, SekelskyJ (2011) Three structure-selective endonucleases are essential in the absence of BLM helicase in Drosophila. PLoS Genet 7: e1002315.

78. YildizO, MajumderS, KramerB, SekelskyJJ (2002) Drosophila MUS312 interacts with the nucleotide excision repair endonuclease MEI-9 to generate meiotic crossovers. Mol Cell 10: 1503–1509.

79. BranzeiD, FoianiM (2007) Interplay of replication checkpoints and repair proteins at stalled replication forks. DNA Repair (Amst) 6: 994–1003.

80. BachratiCZ, BortsRH, HicksonID (2006) Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res 34: 2269–2279.

81. LoYC, PaffettKS, AmitO, ClikemanJA, SterkR, et al. (2006) Sgs1 regulates gene conversion tract lengths and crossovers independently of its helicase activity. Mol Cell Biol 26: 4086–4094.

82. RogersE, BishopJD, WaddleJA, SchumacherJM, LinR (2002) The aurora kinase AIR-2 functions in the release of chromosome cohesion in Caenorhabditis elegans meiosis. J Cell Biol 157: 219–229.

83. BishopJD, HanZ, SchumacherJM (2005) The Caenorhabditis elegans Aurora B kinase AIR-2 phosphorylates and is required for the localization of a BimC kinesin to meiotic and mitotic spindles. Mol Biol Cell 16: 742–756.

84. PasierbekP, JantschM, MelcherM, SchleifferA, SchweizerD, et al. (2001) A Caenorhabditis elegans cohesion protein with functions in meiotic chromosome pairing and disjunction. Genes Dev 15: 1349–1360.

85. SmolikovS, Schild-PrufertK, ColaiacovoMP (2009) A yeast two-hybrid screen for SYP-3 interactors identifies SYP-4, a component required for synaptonemal complex assembly and chiasma formation in Caenorhabditis elegans meiosis. PLoS Genet 5: e1000669.

86. de CarvalhoCE, ZaaijerS, SmolikovS, GuY, SchumacherJM, et al. (2008) LAB-1 antagonizes the Aurora B kinase in C. elegans. Genes Dev 22: 2869–2885.

87. BrennerS (1974) The genetics of Caenorhabditis elegans. Genetics 77: 71–94.

88. JonesMR, LohnZ, RoseAM (2011) Specialized chromosomes and their uses in Caenorhabditis elegans. Methods Cell Biol 106: 23–64.

89. PraitisV, CaseyE, CollarD, AustinJ (2001) Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157: 1217–1226.

90. MacQueenAJ, PhillipsCM, BhallaN, WeiserP, VilleneuveAM, et al. (2005) Chromosome sites play dual roles to establish homologous synapsis during meiosis in C. elegans. Cell 123: 1037–1050.

91. SchermellehL, CarltonPM, HaaseS, ShaoL, WinotoL, et al. (2008) Subdiffraction multicolor imaging of the nuclear periphery with 3D structured illumination microscopy. Science 320: 1332–1336.

92. PoschM, KhoudoliGA, SwiftS, KingEM, DelucaJG, et al. (2010) Sds22 regulates aurora B activity and microtubule-kinetochore interactions at mitosis. J Cell Biol 191: 61–74.

93. GustafssonMG, ShaoL, CarltonPM, WangCJ, GolubovskayaIN, et al. (2008) Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination. Biophys J 94: 4957–4970.

94. WagnerCR, KuerversL, BaillieDL, YanowitzJL (2010) xnd-1 regulates the global recombination landscape in Caenorhabditis elegans. Nature 467: 839–843.