#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Interplay between Structure-Specific Endonucleases for Crossover Control during Meiosis


The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.


Vyšlo v časopise: Interplay between Structure-Specific Endonucleases for Crossover Control during Meiosis. PLoS Genet 9(7): e32767. doi:10.1371/journal.pgen.1003586
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003586

Souhrn

The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.


Zdroje

1. HollidayR (1964) A mechanism for gene conversion in fungi. Genetical Research 5: 282–304.

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

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

4. SinghTR, AliAM, BusyginaV, RaynardS, FanQ, et al. (2008) BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome. Genes Dev 22: 2856–2868.

5. XuD, GuoR, SobeckA, BachratiCZ, YangJ, et al. (2008) RMI, a new OB-fold complex essential for Bloom syndrome protein to maintain genome stability. Genes Dev 22: 2843–2855.

6. MullenJR, KaliramanV, IbrahimSS, BrillSJ (2001) Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics 157: 103–118.

7. 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.

8. ChenXB, MelchionnaR, DenisCM, GaillardPH, BlasinaA, et al. (2001) Human Mus81-associated endonuclease cleaves Holliday junctions in vitro. Mol Cell 8: 1117–1127.

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

10. 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.

11. 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.

12. 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.

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

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

15. DaviesAA, FriedbergEC, TomkinsonAE, WoodRD, WestSC (1995) Role of the Rad1 and Rad10 proteins in nucleotide excision repair and recombination. J Biol Chem 270: 24638–24641.

16. 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.

17. 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.

18. 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.

19. NottkeAC, Beese-SimsSE, PantalenaLF, ReinkeV, ShiY, et al. (2011) SPR-5 is a histone H3K4 demethylase with a role in meiotic double-strand break repair. Proc Natl Acad Sci U S A 108: 12805–12810.

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

21. 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.

22. 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.

23. 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.

24. PanJ, KeeneyS (2007) Molecular cartography: mapping the landscape of meiotic recombination. PLoS Biol 5: e333.

25. BarnesTM, KoharaY, CoulsonA, HekimiS (1995) Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. Genetics 141: 159–179.

26. RockmanMV, KruglyakL (2009) Recombinational landscape and population genomics of Caenorhabditis elegans. PLoS Genet 5: e1000419.

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

28. MeneelyPM, McGovernOL, HeinisFI, YanowitzJL (2012) Crossover distribution and frequency are regulated by him-5 in Caenorhabditis elegans. Genetics 190: 1251–1266.

29. InterthalH, HeyerWD (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.

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

31. CoulonS, GaillardPH, ChahwanC, McDonaldWH, YatesJR3rd, 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.

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

33. HodgkinJ, HorvitzHR, BrennerS (1979) Nondisjunction mutants of the nematode Caenorhabditis elegans. Genetics 91: 67–94.

34. NabeshimaK, VilleneuveAM, HillersKJ (2004) Chromosome-wide regulation of meiotic crossover formation in Caenorhabditis elegans requires properly assembled chromosome axes. Genetics 168: 1275–1292.

35. O'NeilNJ, MartinJS, YoudsJL, WardJD, PetalcorinMI, et al. (2013) Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during C. elegans meiosis. PLoS Genet 9: e1003582.

36. MeneelyPM, FaragoAF, KauffmanTM (2002) Crossover distribution and high interference for both the X chromosome and an autosome during oogenesis and spermatogenesis in Caenorhabditis elegans. Genetics 162: 1169–1177.

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

38. AgostinhoA, MeierB, SonnevilleR, JagutM, WoglarA, et al. (2013) Combinatorial regulation of meiotic Holliday junction resolution in C. elegans by HIM-6/(BLM) helicase, SLX-4, and SLX-1, MUS-81 and XPF-1 nucleases. PLoS Genet 9: e1003591.

39. 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.

40. 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.

41. 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.

42. SchumacherJM, GoldenA, DonovanPJ (1998) AIR-2: An Aurora/Ipl1-related protein kinase associated with chromosomes and midbody microtubules is required for polar body extrusion and cytokinesis in Caenorhabditis elegans embryos. J Cell Biol 143: 1635–1646.

43. 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.

44. AdamoA, CollisSJ, AdelmanCA, SilvaN, HorejsiZ, et al. (2010) Preventing nonhomologous end joining suppresses DNA repair defects of Fanconi anemia. Mol Cell 39: 25–35.

45. AllardP, ColaiacovoMP (2010) Bisphenol A impairs the double-strand break repair machinery in the germline and causes chromosome abnormalities. Proc Natl Acad Sci U S A 107: 20405–20410.

46. MartinJS, WinkelmannN, PetalcorinMI, McIlwraithMJ, BoultonSJ (2005) RAD-51-dependent and -independent roles of a Caenorhabditis elegans BRCA2-related protein during DNA double-strand break repair. Mol Cell Biol 25: 3127–3139.

47. RinaldoC, BazzicalupoP, EderleS, HilliardM, La VolpeA (2002) Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics 160: 471–479.

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

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

50. LemmensBB, TijstermanM (2011) DNA double-strand break repair in Caenorhabditis elegans. Chromosoma 120: 1–21.

51. LemmensBB, JohnsonNM, TijstermanM (2013) COM-1 Promotes Homologous Recombination during Caenorhabditis elegans Meiosis by Antagonizing Ku-Mediated Non-Homologous End Joining. PLoS Genet 9: e1003276.

52. NishantKT, PlysAJ, AlaniE (2008) A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae. Genetics 179: 747–755.

53. BondCS, KvaratskheliaM, RichardD, WhiteMF, HunterWN (2001) Structure of Hjc, a Holliday junction resolvase, from Sulfolobus solfataricus. Proc Natl Acad Sci U S A 98: 5509–5514.

54. HedeMS, PetersenRL, FrohlichRF, KrugerD, AndersenFF, et al. (2007) Resolution of Holliday junction substrates by human topoisomerase I. J Mol Biol 365: 1076–1092.

55. SekiguchiJ, SeemanNC, ShumanS (1996) Resolution of Holliday junctions by eukaryotic DNA topoisomerase I. Proc Natl Acad Sci U S A 93: 785–789.

56. SalewskyB, SchmiesterM, SchindlerD, DigweedM, DemuthI (2012) The nuclease hSNM1B/Apollo is linked to the Fanconi anemia pathway via its interaction with FANCP/SLX4. Hum Mol Genet 21: 4948–56.

57. MeierB, BarberLJ, LiuY, ShtesselL, BoultonSJ, et al. (2009) The MRT-1 nuclease is required for DNA crosslink repair and telomerase activity in vivo in Caenorhabditis elegans. EMBO J 28: 3549–3563.

58. GersteinMB, LuZJ, Van NostrandEL, ChengC, ArshinoffBI, et al. (2010) Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 330: 1775–1787.

59. IkegamiK, EgelhoferTA, StromeS, LiebJD (2010) Caenorhabditis elegans chromosome arms are anchored to the nuclear membrane via discontinuous association with LEM-2. Genome Biol 11: R120.

60. LiuT, RechtsteinerA, EgelhoferTA, VielleA, LatorreI, et al. (2011) Broad chromosomal domains of histone modification patterns in C. elegans. Genome Res 21: 227–236.

61. OsmanF, DixonJ, DoeCL, WhitbyMC (2003) Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Mol Cell 12: 761–774.

62. HollingsworthNM, BrillSJ (2004) The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions. Genes Dev 18: 117–125.

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

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

65. DavisMW, HammarlundM, HarrachT, HullettP, OlsenS, et al. (2005) Rapid single nucleotide polymorphism mapping in C. elegans. BMC Genomics 6: 118.

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

67. WalhoutAJ, VidalM (2001) High-throughput yeast two-hybrid assays for large-scale protein interaction mapping. Methods 24: 297–306.

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

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 7
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#