Chromosome Research

, Volume 15, Issue 5, pp 591–605 | Cite as

ZMM proteins during meiosis: Crossover artists at work

Article

Abstract

Faithful segregation of homologous chromosomes (homologs) during meiosis depends on chiasmata which correspond to crossovers between parental DNA strands. Crossover forming homologous recombination takes place in the context of the synaptonemal complex (SC), a proteinaceous structure that juxtaposes homologs. The coordination between molecular recombination events and assembly of the SC as a structure that provides global connectivity between homologs represents one of the remarkable features of meiosis. ZMM proteins (also known as the synapsis initiation complex  =  SIC) play crucial roles in both processes providing a link between recombination and SC assembly. The ZMM group includes at least seven functionally collaborating, yet structurally diverse proteins: The transverse filament protein Zip1 establishes stable homolog juxtaposition by polymerizing as an integral component of the SC. Zip2, Zip3, and Zip4 likely mediate protein–protein interactions, while Mer3, Msh4, and Msh5 directly promote steps in DNA recombination. This review focuses on recent insights into ZMM functions in yeast meiosis and draws comparisons to ZMM-related proteins in other model organisms.

Key words

double Holliday junctions meiosis recombination stable strand invasion ZMM proteins 

References

  1. Agarwal S, Roeder GS (2000) Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102: 245–255.PubMedCrossRefGoogle Scholar
  2. Allers T, Lichten M (2001) Differential timing and control of noncrossover and crossover recombination during meiosis. Cell 106: 47–57.PubMedCrossRefGoogle Scholar
  3. Alpi A, Pasierbek P, Gartner A, Loidl J (2003) Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans. Chromosoma 112: 6–16.PubMedCrossRefGoogle Scholar
  4. Argueso JL, Wanat J, Gemici Z, Alani E (2004) Competing crossover pathways act during meiosis in Saccharomyces cerevisiae. Genetics 168: 1805–1816.PubMedCrossRefGoogle Scholar
  5. Bishop DK, Park D, Xu L, Kleckner N (1992) DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell 69: 439–456.PubMedCrossRefGoogle Scholar
  6. Bishop DK (1994) RecA homologs Dmc1 and Rad51 interact to form multiple nuclear complexes prior to meiotic chromosome synapsis. Cell 79: 1081–1092.PubMedCrossRefGoogle Scholar
  7. Bishop DK, Zickler D (2004) Early decision; meiotic crossover interference prior to stable strand exchange and synapsis. Cell 117: 9–15.PubMedCrossRefGoogle Scholar
  8. Börner GV, Kleckner N, Hunter N (2004) Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117: 29–45.PubMedCrossRefGoogle Scholar
  9. Carpenter AT (1987) Gene conversion, recombination nodules, and the initiation of meiotic synapsis. Bioessays 6: 232–236.PubMedCrossRefGoogle Scholar
  10. Chelysheva L, Gendrot G, Vezon D, et al. (2007) Zip4/Spo22 is required for class I CO formation but not for synapsis completion in Arabidopsis thaliana. PLoS Genet. 3:e83.PubMedCrossRefGoogle Scholar
  11. Chen C, Zhang W, Timofejeva L, Gerardin Y, Ma H (2005) The Arabidopsis ROCK-N-ROLLERS gene encodes a homolog of the yeast ATP-dependent DNA helicase MER3 and is required for normal meiotic crossover formation. Plant J 43: 321–334.PubMedCrossRefGoogle Scholar
  12. Cheng CH, Lo YH, Liang SS, et al. (2006) SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes Dev 20: 2067–2081.PubMedCrossRefGoogle Scholar
  13. Chua PR, Roeder GS (1998) Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell 93: 349–359.PubMedCrossRefGoogle Scholar
  14. Colaiacovo MP, MacQueen AJ, Martinez-Perez E, 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.PubMedCrossRefGoogle Scholar
  15. Copenhaver GP (2005) Plant genetics: when not to interfere. Curr Biol. 15: R290–291.PubMedCrossRefGoogle Scholar
  16. de Boer E, Heyting C (2006) The diverse roles of transverse filaments of synaptonemal complexes in meiosis. Chromosoma 115: 220–234.PubMedCrossRefGoogle Scholar
  17. de Boer E, Dietrich AJ, Hoog C, Stam P, Heyting C (2007) Meiotic interference among MLH1 foci requires neither an intact axial element structure nor full synapsis. J Cell Sci 120: 731–736.PubMedCrossRefGoogle Scholar
  18. de Boer E, Stam P, Dietrich AJ, Pastink A, Heyting C (2006) Two levels of interference in mouse meiotic recombination. Proc Natl Acad Sci USA 103: 9607–9612.PubMedCrossRefGoogle Scholar
  19. de los Santos T, Hunter N, Lee C, Larkin B, Loidl J, Hollingsworth NM (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.PubMedGoogle Scholar
  20. de Vries SS, Baart EB, Dekker M, Siezen A, de Rooij DG, de Boer P, te Riele H (1999) Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis. Genes Dev 13: 523–531.PubMedGoogle Scholar
  21. de Vries FA, de Boer E, van den Bosch M, et al. (2005) Mouse Sycp1 functions in synaptonemal complex assembly, meiotic recombination, and XY body formation. Genes Dev 19: 1376–1389.PubMedCrossRefGoogle Scholar
  22. Edelmann W, Cohen PE, Kneitz B, et al. (1999) Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat Genet 21: 123–127.PubMedCrossRefGoogle Scholar
  23. Fung JC, Rockmill B, Odell M, Roeder GS (2004) Imposition of crossover interference through the nonrandom distribution of synapsis initiation complexes. Cell 116: 795–802.PubMedCrossRefGoogle Scholar
  24. Guillon H, Baudat F, Grey C, Liskay RM, de Massy B (2005) Crossover and noncrossover pathways in mouse meiosis. Mol Cell 20: 563–573.PubMedCrossRefGoogle Scholar
  25. Hassold T, Hunt P (2001) To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2: 280–291.PubMedCrossRefGoogle Scholar
  26. Henderson KA, Keeney S (2004) Tying synaptonemal complex initiation to the formation and programmed repair of DNA double-strand breaks. Proc Natl Acad Sci USA 101: 4519–4524.PubMedCrossRefGoogle Scholar
  27. Higgins JD, Armstrong SJ, Franklin FC, Jones GH (2004) The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. Genes Dev 18: 2557–2570.PubMedCrossRefGoogle Scholar
  28. Higgins JD, Sanchez-Moran E, Armstrong SJ, Jones GH, Franklin FC (2005) The Arabidopsis synaptonemal complex protein ZYP1 is required for chromosome synapsis and normal fidelity of crossing over. Genes Dev 19: 2488–2500.PubMedCrossRefGoogle Scholar
  29. Hollingsworth NM, Ponte L, Halsey C (1995) MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev 9: 1728–1739.PubMedCrossRefGoogle Scholar
  30. Hooker GW, Roeder GS (2006) A role for SUMO in meiotic chromosome synapsis. Curr Biol 16: 1238–1243.PubMedCrossRefGoogle Scholar
  31. Hunter N, Kleckner N (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.PubMedCrossRefGoogle Scholar
  32. Jantsch V, Pasierbek P, Mueller MM, Schweizer D, Jantsch M, Loidl J (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.PubMedCrossRefGoogle Scholar
  33. Jessop L, Rockmill B, Roeder GS, Lichten M (2006) Meiotic chromosome synapsis-promoting proteins antagonize the anti-crossover activity of sgs1. PLoS Genet. 2: e155.PubMedCrossRefGoogle Scholar
  34. Kelly KO, Dernburg AF, Stanfield GM, Villeneuve AM (2000) Caenorhabditis elegans msh-5 is required for both normal and radiation-induced meiotic crossing over but not for completion of meiosis. Genetics 156: 617–630.PubMedGoogle Scholar
  35. Kerscher O, Felberbaum R, Hochstrasser M (2006) Modification of proteins by ubiquitin and ubiquitin-like proteins. Annu Rev Cell Dev Biol 22: 159–180.PubMedCrossRefGoogle Scholar
  36. Kneitz B, Cohen PE, Avdievich E, et al. (2000) MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev 14: 1085–1097.PubMedGoogle Scholar
  37. Lynn A, Ashley T, Hassold T (2004) Variation in human meiotic recombination. Annu Rev Genomics Hum Genet 5: 317–349.PubMedCrossRefGoogle Scholar
  38. MacQueen AJ, Colaiacovo MP, McDonald K, Villeneuve AM (2002) Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans. Genes Dev 16: 2428–2442.PubMedCrossRefGoogle Scholar
  39. Mahadevaiah SK, Turner JM, Baudat F, et al. (2001) Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet 27: 271–276.PubMedCrossRefGoogle Scholar
  40. Marcon E, Moens P (2003) MLH1p and MLH3p localize to precociously induced chiasmata of okadaic-acid-treated mouse spermatocytes. Genetics 165: 2283–2287.PubMedGoogle Scholar
  41. Martini E, Diaz RL, Hunter N, Keeney S (2006) Crossover homeostasis in yeast meiosis. Cell 126: 285–295.PubMedCrossRefGoogle Scholar
  42. Mazina OM, Mazin AV, Nakagawa T, Kolodner RD, Kowalczykowski SC (2004) Saccharomyces cerevisiae Mer3 helicase stimulates 3′–5′ heteroduplex extension by Rad51; implications for crossover control in meiotic recombination. Cell 117: 47–56.PubMedCrossRefGoogle Scholar
  43. Mercier R, Jolivet S, Vezon D, et al. (2005) Two meiotic crossover classes cohabit in Arabidopsis: one is dependent on MER3, whereas the other one is not. Curr Biol 15: 692–701.PubMedCrossRefGoogle Scholar
  44. Mitra N, Roeder GS (2007) A novel non-null ZIP1 allele triggers meiotic arrest with synapsed chromosomes in S. cerevisiae. Genetics 176: 773–787.PubMedCrossRefGoogle Scholar
  45. Moens PB, Kolas NK, Tarsounas M, Marcon E, Cohen PE, Spyropoulos B (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 15: 1611–1622.Google Scholar
  46. Nakagawa T, Kolodner RD (2002) Saccharomyces cerevisiae Mer3 is a DNA helicase involved in meiotic crossing over. Mol Cell Biol 22: 3281–3291.PubMedCrossRefGoogle Scholar
  47. Nakagawa T, Flores-Rozas H, Kolodner RD (2001) The MER3 helicase involved in meiotic crossing over is stimulated by single-stranded DNA-binding proteins and unwinds DNA in the 3′ to 5′ direction. J Biol Chem 276: 31487–31493.PubMedCrossRefGoogle Scholar
  48. Nakagawa T, Ogawa H (1999) The Saccharomyces cerevisiae MER3 gene, encoding a novel helicase-like protein, is required for crossover control in meiosis. EMBO J 18: 5714–5723.PubMedCrossRefGoogle Scholar
  49. Neyton S, Lespinasse F, Moens PB, et al. (2004) Association between MSH4 (MutS homologue 4) and the DNA strand-exchange RAD51 and DMC1 proteins during mammalian meiosis. Mol Hum Reprod 10: 917–924.PubMedCrossRefGoogle Scholar
  50. Novak JE, Ross-Macdonald PB, Roeder GS (2001) The budding yeast Msh4 protein functions in chromosome synapsis and the regulation of crossover distribution. Genetics 158: 1013–1025.PubMedGoogle Scholar
  51. Padmore R, Cao L, Kleckner N (1991) Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell 66: 1239–1256.PubMedCrossRefGoogle Scholar
  52. Page SL, Hawley RS (2004) The genetics and molecular biology of the synaptonemal complex. Annu Rev Cell Dev Biol 20: 525–558.PubMedCrossRefGoogle Scholar
  53. Perry J, Kleckner N, Börner GV (2005) Bioinformatic analyses implicate the collaborating meiotic crossover/chiasma proteins Zip2, Zip3, and Spo22/Zip4 in ubiquitin labeling. Proc Natl Acad Sci USA 102: 17594–17599.PubMedCrossRefGoogle Scholar
  54. Rockmill B, Fung JC, Branda SS, Roeder GS (2003) The Sgs1 helicase regulates chromosome synapsis and meiotic crossing over. Curr Biol 13: 1954–1962.PubMedCrossRefGoogle Scholar
  55. Schwacha A, Kleckner N (1995) Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83: 783–791.PubMedCrossRefGoogle Scholar
  56. Schwacha A, Kleckner N (1997) Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway. Cell 90: 1123–1135.PubMedCrossRefGoogle Scholar
  57. Snowden T, Acharya S, Butz C, Berardini M, Fishel R (2004) hMSH4-hMSH5 recognizes Holliday junctions and forms a meiosis-specific sliding clamp that embraces homologous chromosomes. Mol Cell 15: 437–451.PubMedCrossRefGoogle Scholar
  58. Storlazzi A, Xu L, Schwacha A, Kleckner N (1996) Synaptonemal complex (SC) component Zip1 plays a role in meiotic recombination independent of SC polymerization along the chromosomes. Proc Natl Acad Sci USA 93: 9043–9048.PubMedCrossRefGoogle Scholar
  59. Sun H, Treco D, Schultes NP, Szostak JW (1989) Double-strand breaks at an initiation site for meiotic gene conversion. Nature 338: 87–90.PubMedCrossRefGoogle Scholar
  60. Sym M, Engebrecht JA, Roeder GS (1993) ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis. Cell 72: 365–378.PubMedCrossRefGoogle Scholar
  61. Sym M, Roeder GS (1994) Crossover interference is abolished in the absence of a synaptonemal complex protein. Cell 79: 283–292.PubMedCrossRefGoogle Scholar
  62. Tanaka K, Miyamoto N, Shouguchi-Miyata J, Ikeda JE (2006) HFM1, the human homologue of yeast Mer3, encodes a putative DNA helicase expressed specifically in germ-line cells. DNA Seq 17: 226–242.Google Scholar
  63. Tease C, Hartshorne GM, Hulten MA (2002) Patterns of meiotic recombination in human fetal oocytes. Am J Hum Genet 70: 1469–1479.PubMedCrossRefGoogle Scholar
  64. Tsubouchi T, Zhao H, Roeder GS (2006) The meiosis-specific Zip4 protein regulates crossover distribution by promoting synaptonemal complex formation together with Zip2. Dev Cell 10: 809–819.PubMedCrossRefGoogle Scholar
  65. Zalevsky J, MacQueen AJ, Duffy JB, Kemphues KJ, Villeneuve AM (1999) Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast. Genetics 153: 1271–1283.PubMedGoogle Scholar
  66. Zickler D, Kleckner N (1999) Meiotic chromosomes: integrating structure and function. Annu Rev Genet 33: 603–754.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2007

Authors and Affiliations

  • Audrey Lynn
    • 1
  • Rachel Soucek
    • 1
  • G. Valentin Börner
    • 1
  1. 1.Department of Biological, Geological and Environmental SciencesCleveland State UniversityClevelandUSA

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