Smc5/6 Coordinates Formation and Resolution of Joint Molecules with Chromosome Morphology to Ensure Meiotic Divisions

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During meiosis, Structural Maintenance of Chromosome (SMC) complexes underpin two fundamental features of meiosis: homologous recombination and chromosome segregation. While meiotic functions of the cohesin and condensin complexes have been delineated, the role of the third SMC complex, Smc5/6, remains enigmatic. Here we identify specific, essential meiotic functions for the Smc5/6 complex in homologous recombination and the regulation of cohesin. We show that Smc5/6 is enriched at centromeres and cohesin-association sites where it regulates sister-chromatid cohesion and the timely removal of cohesin from chromosomal arms, respectively. Smc5/6 also localizes to recombination hotspots, where it promotes normal formation and resolution of a subset of joint-molecule intermediates. In this regard, Smc5/6 functions independently of the major crossover pathway defined by the MutLγ complex. Furthermore, we show that Smc5/6 is required for stable chromosomal localization of the XPF-family endonuclease, Mus81-Mms4^Eme1. Our data suggest that the Smc5/6 complex is required for specific recombination and chromosomal processes throughout meiosis and that in its absence, attempts at cell division with unresolved joint molecules and residual cohesin lead to severe recombination-induced meiotic catastrophe.

Vyšlo v časopise: Smc5/6 Coordinates Formation and Resolution of Joint Molecules with Chromosome Morphology to Ensure Meiotic Divisions. PLoS Genet 9(12): e32767. doi:10.1371/journal.pgen.1004071
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004071

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1. NealeMJ, KeeneyS (2006) Clarifying the mechanics of DNA strand exchange in meiotic recombination. Nature 442: 153–158.

2. HendersonKA, KeeneyS (2004) Tying synaptonemal complex initiation to the formation and programmed repair of DNA double-strand breaks. Proc Natl Acad Sci U S A 101: 4519–4524.

3. KitajimaTS, KawashimaSA, WatanabeY (2004) The conserved kinetochore protein shugoshin protects centromeric cohesion during meiosis. Nature 427: 510–517.

4. MarstonAL, ThamWH, ShahH, AmonA (2004) A genome-wide screen identifies genes required for centromeric cohesion. Science 303: 1367–1370.

5. GreganJ, RabitschPK, SakemB, CsutakO, LatypovV, et al. (2005) Novel genes required for meiotic chromosome segregation are identified by a high-throughput knockout screen in fission yeast. Curr Biol 15: 1663–1669.

6. XuL, AjimuraM, PadmoreR, KleinC, KlecknerN (1995) NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces cerevisiae. Mol Cell Biol 15: 6572–6581.

7. ClyneRK, KatisVL, JessopL, BenjaminKR, HerskowitzI, et al. (2003) Polo-like kinase Cdc5 promotes chiasmata formation and cosegregation of sister centromeres at meiosis I. Nat Cell Biol 5: 480–485.

8. SourirajanA, LichtenM (2008) Polo-like kinase Cdc5 drives exit from pachytene during budding yeast meiosis. Genes Dev 22: 2627–2632.

9. McMahillMS, ShamCW, BishopDK (2007) Synthesis-dependent strand annealing in meiosis. PLoS Biol 5: e299.

10. OhSD, LaoJP, HwangPY, TaylorAF, SmithGR, et al. (2007) BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell 130: 259–272.

11. JessopL, LichtenM (2008) Mus81/Mms4 endonuclease and Sgs1 helicase collaborate to ensure proper recombination intermediate metabolism during meiosis. Mol Cell 31: 313–323.

12. OhSD, LaoJP, TaylorAF, SmithGR, HunterN (2008) RecQ helicase, Sgs1, and XPF family endonuclease, Mus81-Mms4, resolve aberrant joint molecules during meiotic recombination. Mol Cell 31: 324–336.

13. 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.

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

15. MullenJR, NallasethFS, LanYQ, SlagleCE, BrillSJ (2005) Yeast Rmi1/Nce4 controls genome stability as a subunit of the Sgs1-Top3 complex. Mol Cell Biol 25: 4476–4487.

16. WuL, BachratiCZ, OuJ, XuC, YinJ, et al. (2006) BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates. Proc Natl Acad Sci U S A 103: 4068–4073.

17. HoffmannER, BortsRH (2004) Meiotic recombination intermediates and mismatch repair proteins. Cytogenet Genome Res 107: 232–248.

18. KolasNK, CohenPE (2004) Novel and diverse functions of the DNA mismatch repair family in mammalian meiosis and recombination. Cytogenet Genome Res 107: 216–231.

19. SnowdenT, AcharyaS, ButzC, BerardiniM, FishelR (2004) hMSH4-hMSH5 recognizes Holliday Junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes. Mol Cell 15: 437–451.

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

21. JessopL, RockmillB, RoederGS, LichtenM (2006) Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of Sgs1. PLoS Genet 2: e155.

22. 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.

23. 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.

24. ZalevskyJ, MacQueenAJ, DuffyJB, KemphuesKJ, VilleneuveAM (1999) Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast. Genetics 153: 1271–1283.

25. KohlKP, JonesCD, SekelskyJ (2012) Evolution of an MCM complex in flies that promotes meiotic crossovers by blocking BLM helicase. Science 338: 1363–1365.

26. 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.

27. SmithGR, BoddyMN, ShanahanP, RussellP (2003) Fission yeast Mus81-Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics 165: 2289–2293.

28. 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.

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

30. de los SantosT, HunterN, LeeC, LarkinB, LoidlJ, et al. (2003) The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 164: 81–94.

31. BerchowitzLE, FrancisKE, BeyAL, CopenhaverGP (2007) The role of AtMUS81 in interference-insensitive crossovers in A. thaliana. PLoS Genet 3: e132.

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

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

34. FrickeWM, BrillSJ (2003) Slx1–Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes Dev 17: 1768–1778.

35. 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.

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

37. WoodAJ, SeversonAF, MeyerBJ (2010) Condensin and cohesin complexity: the expanding repertoire of functions. Nat Rev Genet 11: 391–404.

38. AmpatzidouE, IrmischA, O'ConnellMJ, MurrayJM (2006) Smc5/6 is required for repair at collapsed replication forks. Mol Cell Biol 26: 9387–9401.

39. SheedyDM, DimitrovaD, RankinJK, BassKL, LeeKM, et al. (2005) Brc1-mediated DNA repair and damage tolerance. Genetics 171: 457–468.

40. Torres-RosellJ, MachinF, FarmerS, JarmuzA, EydmannT, et al. (2005) SMC5 and SMC6 genes are required for the segregation of repetitive chromosome regions. Nat Cell Biol 7: 412–419.

41. ChenYH, ChoiK, SzakalB, ArenzJ, DuanX, et al. (2009) Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci U S A 106: 21252–21257.

42. ChavezA, AgrawalV, JohnsonFB (2011) Homologous recombination-dependent rescue of deficiency in the structural maintenance of chromosomes (Smc) 5/6 complex. J Biol Chem 286: 5119–5125.

43. MurrayJM, CarrAM (2008) Smc5/6: a link between DNA repair and unidirectional replication? Nat Rev Mol Cell Biol 9: 177–182.

44. IrmischA, AmpatzidouE, MizunoK, O'ConnellMJ, MurrayJM (2009) Smc5/6 maintains stalled replication forks in a recombination-competent conformation. EMBO J 28: 144–155.

45. Bermudez-LopezM, CeschiaA, de PiccoliG, ColominaN, PaseroP, et al. (2010) The Smc5/6 complex is required for dissolution of DNA-mediated sister chromatid linkages. Nucleic Acids Res 38: 6502–6512.

46. ZhaoX, BlobelG (2005) A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A 102: 4777–4782.

47. AndrewsEA, PalecekJ, SergeantJ, TaylorE, LehmannAR, et al. (2005) Nse2, a component of the Smc5–6 complex, is a SUMO ligase required for the response to DNA damage. Mol Cell Biol 25: 185–196.

48. PottsPR, YuH (2005) Human MMS21/NSE2 is a SUMO ligase required for DNA repair. Mol Cell Biol 25: 7021–7032.

49. PottsPR, YuH (2007) The SMC5/6 complex maintains telomere length in ALT cancer cells through sumoylation of telomere-binding proteins. Nat Struct Mol Biol 14: 581–590.

50. McAleenanA, Cordon-PreciadoV, Clemente-BlancoA, LiuIC, SenN, et al. (2012) Sumoylation of the alpha-kleisin subunit of cohesin is required for DNA damage-induced cohesion. Curr Biol: CB 22: 1564–1575.

51. WuN, KongX, JiZ, ZengW, PottsPR, et al. (2012) Scc1 sumoylation by Mms21 promotes sister chromatid recombination through counteracting Wapl. Genes Dev 26: 1473–1485.

52. HangLE, LiuX, CheungI, YangY, ZhaoX (2011) SUMOylation regulates telomere length homeostasis by targeting Cdc13. Nat Struct Mol Biol 18: 920–926.

53. ChenYH, ChoiK, SzakalB, ArenzJ, DuanX, et al. (2009) Interplay between the Smc5/6 complex and the Mph1 helicase in recombinational repair. Proc Natl Acad Sci U S A 106: 21252–21257.

54. FarmerS, San-SegundoPA, AragonL (2011) The Smc5–Smc6 complex is required to remove chromosome junctions in meiosis. PLoS One 6: e20948.

55. Wehrkamp-RichterS, HyppaRW, PruddenJ, SmithGR, BoddyMN (2012) Meiotic DNA joint molecule resolution depends on Nse5–Nse6 of the Smc5–Smc6 holocomplex. Nucleic Acids Res 40: 9633–9646.

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

57. GaskellLJ, OsmanF, GilbertRJ, WhitbyMC (2007) Mus81 cleavage of Holliday junctions: a failsafe for processing meiotic recombination intermediates? EMBO J 26: 1891–1901.

58. 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.

59. AndersenSL, SekelskyJ (2010) Meiotic versus mitotic recombination: two different routes for double-strand break repair: the different functions of meiotic versus mitotic DSB repair are reflected in different pathway usage and different outcomes. BioEssays 32: 1058–1066.

60. LindroosHB, StromL, ItohT, KatouY, ShirahigeK, et al. (2006) Chromosomal association of the Smc5/6 complex reveals that it functions in differently regulated pathways. Mol Cell 22: 755–767.

61. XaverM, HuangL, ChengD, KleinF (2013) Smc5/6-Mms21 prevents and eliminates inappropriate recombination intermediates in meiosis. PLoS Genet 10: e1004067.

62. BlatY, KlecknerN (1999) Cohesins bind to preferential sites along yeast chromosome III, with differential regulation along arms versus the centric region. Cell 98: 249–259.

63. PanizzaS, MendozaMA, BerlingerM, HuangL, NicolasA, et al. (2011) Spo11-accessory proteins link double-strand break sites to the chromosome axis in early meiotic recombination. Cell 146: 372–383.

64. 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.

65. BlitzblauHG, BellGW, RodriguezJ, BellSP, HochwagenA (2007) Mapping of meiotic single-stranded DNA reveals double-stranded-break hotspots near centromeres and telomeres. Curr Biol 17: 2003–2012.

66. 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.

67. ChuS, DeRisiJ, EisenM, MulhollandJ, BotsteinD, et al. (1998) The transcriptional program of sporulation in budding yeast. Science 282: 699–705.

68. ChanAC, BortsRH, HoffmannE (2009) Temperature-dependent modulation of chromosome segregation in msh4 mutants of budding yeast. PLoS One 4: e7284.

69. NishimuraK, FukagawaT, TakisawaH, KakimotoT, KanemakiM (2009) An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat Methods 6: 917–922.

70. PalecekJ, VidotS, FengM, DohertyAJ, LehmannAR (2006) The Smc5–Smc6 DNA repair complex. bridging of the Smc5–Smc6 heads by the kleisin, Nse4, and non-Kleisin subunits. J Biol Chem 281: 36952–36959.

71. SchwachaA, KlecknerN (1994) Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. Cell 76: 51–63.

72. HunterN, KlecknerN (2001) The single-end invasion: an asymmetric intermediate at the double- strand break to double-holliday junction transition of meiotic recombination. Cell 106: 59–70.

73. LilienthalI, KannoT, SjögrenC (2013) Inhibition of the Smc5/6 complex during meiosis perturbs joint molecule formation and resolution without significantly changing crossover or non-crossover levels. PLoS Genet 9: e1003898.

74. SvetlanovA, CohenPE (2004) Mismatch repair proteins, meiosis, and mice: understanding the complexities of mammalian meiosis. Exp Cell Res 296: 71–79.

75. HunterN, BortsRH (1997) Mlh1p is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev 11: 1573–1582.

76. WattsFZ, HoffmannE (2011) SUMO meets meiosis: an encounter at the synaptonemal complex. Bioessays 33: 529–537.

77. AgarwalS, RoederGS (2000) Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102: 245–255.

78. RockmillB, FungJC, BrandaSS, RoederGS (2003) The Sgs1 helicase regulates chromosome synapsis and meiotic crossing over. Curr Biol 13: 1954–1962.

79. KaliramanV, MullenJR, FrickeWM, Bastin-ShanowerSA, BrillSJ (2001) Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease. Genes Dev 15: 2730–2740.

80. DownsJA, LowndesNF, JacksonSP (2000) A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature 408: 1001–1004.

81. CarballoJA, JohnsonAL, SedgwickSG, ChaRS (2008) Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic interhomolog recombination. Cell 132: 758–770.

82. LeeBH, AmonA (2003) Role of Polo-like kinase CDC5 in programming meiosis I chromosome segregation. Science 300: 482–486.

83. HochwagenA, AmonA (2006) Checking your breaks: surveillance mechanisms of meiotic recombination. Curr Biol 16: R217–228.

84. HochwagenA, ThamWH, BrarGA, AmonA (2005) The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity. Cell 122: 861–873.

85. BuonomoSB, ClyneRK, FuchsJ, LoidlJ, UhlmannF, et al. (2000) Disjunction of homologous chromosomes in meiosis I depends on proteolytic cleavage of the meiotic cohesin Rec8 by separin. Cell 103: 387–398.

86. Tapia-AlvealC, OutwinEA, TrempolecN, DziadkowiecD, MurrayJM, et al. (2010) SMC complexes and topoisomerase II work together so that sister chromatids can work apart. Cell Cycle 9: 2065–2070.

87. OutwinEA, IrmischA, MurrayJM, O'ConnellMJ (2009) Smc5–Smc6-dependent removal of cohesin from mitotic chromosomes. Mol Cell Biol 29: 4363–4375.

88. MatosJ, LippJJ, BogdanovaA, GuillotS, OkazE, et al. (2008) Dbf4-dependent CDC7 kinase links DNA replication to the segregation of homologous chromosomes in meiosis I. Cell 135: 662–678.

89. KimKP, WeinerBM, ZhangL, JordanA, DekkerJ, et al. (2010) Sister cohesion and structural axis components mediate homolog bias of meiotic recombination. Cell 143: 924–937.

90. YuHG, KoshlandDE (2003) Meiotic condensin is required for proper chromosome compaction, SC assembly, and resolution of recombination-dependent chromosome linkages. J Cell Biol 163: 937–947.

91. PebernardS, McDonaldWH, PavlovaY, YatesJR3rd, BoddyMN (2004) Nse1, Nse2, and a novel subunit of the Smc5–Smc6 complex, Nse3, play a crucial role in meiosis. Mol Biol Cell 15: 4866–4876.

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

93. YuHG, KoshlandD (2005) Chromosome morphogenesis: condensin-dependent cohesin removal during meiosis. Cell 123: 397–407.

94. RoyMA, SiddiquiN, D'AmoursD (2011) Dynamic and selective DNA-binding activity of Smc5, a core component of the Smc5–Smc6 complex. Cell Cycle 10: 690–700.

95. BlitzblauHG, ChanCS, HochwagenA, BellSP (2012) Separation of DNA replication from the assembly of break-competent meiotic chromosomes. PLoS Genet 8: e1002643.

96. MurakamiH, BordeV, NicolasA, KeeneyS (2009) Gel electrophoresis assays for analyzing DNA double-strand breaks in Saccharomyces cerevisiae at various spatial resolutions. Methods Mol Biol 557: 117–142.

97. GrayS, AllisonRM, GarciaV, GoldmanAS, NealeMJ (2013) Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR). Open biology 3: 130019.

98. NewnhamL, JordanP, RockmillB, RoederGS, HoffmannE (2010) The synaptonemal complex protein, Zip1, promotes the segregation of nonexchange chromosomes at meiosis I. Proc Natl Acad Sci U S A 107: 781–785.

99. JordanP, CopseyA, NewnhamL, KolarE, LichtenM, et al. (2009) Ipl1/Aurora B kinase coordinates synaptonemal complex disassembly with cell cycle progression and crossover formation in budding yeast meiosis. Genes Dev 23: 2237–2251.

100. VaderG, BlitzblauHG, TameMA, FalkJE, CurtinL, et al. (2011) Protection of repetitive DNA borders from self-induced meiotic instability. Nature 477: 115–119.

101. CarlileTM, AmonA (2008) Meiosis I is established through division-specific translational control of a cyclin. Cell 133: 280–291.