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. 2004 Jun;167(2):593–605. doi: 10.1534/genetics.103.023762

Conserved and nonconserved proteins for meiotic DNA breakage and repair in yeasts.

Jennifer A Young 1, Randy W Hyppa 1, Gerald R Smith 1
PMCID: PMC1470912  PMID: 15238514

Abstract

During meiosis DNA double-strand breaks initiate recombination in the distantly related budding and fission yeasts and perhaps in most eukaryotes. Repair of broken meiotic DNA is essential for formation of viable gametes. We report here distinct but overlapping sets of proteins in these yeasts required for formation and repair of double-strand breaks. Meiotic DNA breakage in Schizosaccharomyces pombe did not require Rad50 or Rad32, although the homologs Rad50 and Mre11 are required in Saccharomyces cerevisiae; these proteins are required for meiotic DNA break repair in both yeasts. DNA breakage required the S. pombe midmeiosis transcription factor Mei4, but the structurally unrelated midmeiosis transcription factor Ndt80 is not required for breakage in S. cerevisiae. Rhp51, Swi5, and Rad22 + Rti1 were required for full levels of DNA repair in S. pombe, as are the related S. cerevisiae proteins Rad51, Sae3, and Rad52. Dmc1 was not required for repair in S. pombe, but its homolog Dmc1 is required in the well-studied strain SK1 of S. cerevisiae. Additional proteins required in one yeast have no obvious homologs in the other yeast. The occurrence of conserved and nonconserved proteins indicates potential diversity in the mechanism of meiotic recombination and divergence of the machinery during the evolution of eukaryotes.

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Selected References

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  1. Abe H., Shimoda C. Autoregulated expression of Schizosaccharomyces pombe meiosis-specific transcription factor Mei4 and a genome-wide search for its target genes. Genetics. 2000 Apr;154(4):1497–1508. doi: 10.1093/genetics/154.4.1497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aboussekhra A., Chanet R., Adjiri A., Fabre F. Semidominant suppressors of Srs2 helicase mutations of Saccharomyces cerevisiae map in the RAD51 gene, whose sequence predicts a protein with similarities to procaryotic RecA proteins. Mol Cell Biol. 1992 Jul;12(7):3224–3234. doi: 10.1128/mcb.12.7.3224. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akamatsu Yufuko, Dziadkowiec Dorota, Ikeguchi Mitsunori, Shinagawa Hideo, Iwasaki Hiroshi. Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast. Proc Natl Acad Sci U S A. 2003 Dec 8;100(26):15770–15775. doi: 10.1073/pnas.2632890100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Alani E., Padmore R., Kleckner N. Analysis of wild-type and rad50 mutants of yeast suggests an intimate relationship between meiotic chromosome synapsis and recombination. Cell. 1990 May 4;61(3):419–436. doi: 10.1016/0092-8674(90)90524-i. [DOI] [PubMed] [Google Scholar]
  5. Allers T., Lichten M. Differential timing and control of noncrossover and crossover recombination during meiosis. Cell. 2001 Jul 13;106(1):47–57. doi: 10.1016/s0092-8674(01)00416-0. [DOI] [PubMed] [Google Scholar]
  6. Arcangioli B. A site- and strand-specific DNA break confers asymmetric switching potential in fission yeast. EMBO J. 1998 Aug 3;17(15):4503–4510. doi: 10.1093/emboj/17.15.4503. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Arcangioli B., de Lahondès R. Fission yeast switches mating type by a replication-recombination coupled process. EMBO J. 2000 Mar 15;19(6):1389–1396. doi: 10.1093/emboj/19.6.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bishop D. K., Park D., Xu L., Kleckner N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell. 1992 May 1;69(3):439–456. doi: 10.1016/0092-8674(92)90446-j. [DOI] [PubMed] [Google Scholar]
  9. Boddy M. N., Gaillard P. H., McDonald W. H., Shanahan P., Yates J. R., 3rd, Russell P. Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell. 2001 Nov 16;107(4):537–548. doi: 10.1016/s0092-8674(01)00536-0. [DOI] [PubMed] [Google Scholar]
  10. Borde Valérie, Lin Waka, Novikov Eugene, Petrini John H., Lichten Michael, Nicolas Alain. Association of Mre11p with double-strand break sites during yeast meiosis. Mol Cell. 2004 Feb 13;13(3):389–401. doi: 10.1016/s1097-2765(04)00034-6. [DOI] [PubMed] [Google Scholar]
  11. Cao L., Alani E., Kleckner N. A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae. Cell. 1990 Jun 15;61(6):1089–1101. doi: 10.1016/0092-8674(90)90072-m. [DOI] [PubMed] [Google Scholar]
  12. Chahwan Charly, Nakamura Toru M., Sivakumar Sasirekha, Russell Paul, Rhind Nicholas. The fission yeast Rad32 (Mre11)-Rad50-Nbs1 complex is required for the S-phase DNA damage checkpoint. Mol Cell Biol. 2003 Sep;23(18):6564–6573. doi: 10.1128/MCB.23.18.6564-6573.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Chu S., DeRisi J., Eisen M., Mulholland J., Botstein D., Brown P. O., Herskowitz I. The transcriptional program of sporulation in budding yeast. Science. 1998 Oct 23;282(5389):699–705. doi: 10.1126/science.282.5389.699. [DOI] [PubMed] [Google Scholar]
  14. De Veaux L. C., Hoagland N. A., Smith G. R. Seventeen complementation groups of mutations decreasing meiotic recombination in Schizosaccharomyces pombe. Genetics. 1992 Feb;130(2):251–262. doi: 10.1093/genetics/130.2.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ding R., Smith G. R. Global control of meiotic recombination genes by Schizosaccharomyces pombe rec16 (rep1). Mol Gen Genet. 1998 Jun;258(6):663–670. doi: 10.1007/s004380050780. [DOI] [PubMed] [Google Scholar]
  16. Fan J. B., Chikashige Y., Smith C. L., Niwa O., Yanagida M., Cantor C. R. Construction of a Not I restriction map of the fission yeast Schizosaccharomyces pombe genome. Nucleic Acids Res. 1989 Apr 11;17(7):2801–2818. doi: 10.1093/nar/17.7.2801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fox M. E., Smith G. R. Control of meiotic recombination in Schizosaccharomyces pombe. Prog Nucleic Acid Res Mol Biol. 1998;61:345–378. doi: 10.1016/s0079-6603(08)60831-4. [DOI] [PubMed] [Google Scholar]
  18. Fukushima K., Tanaka Y., Nabeshima K., Yoneki T., Tougan T., Tanaka S., Nojima H. Dmc1 of Schizosaccharomyces pombe plays a role in meiotic recombination. Nucleic Acids Res. 2000 Jul 15;28(14):2709–2716. doi: 10.1093/nar/28.14.2709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gaillard Pierre-Henri L., Noguchi Eishi, Shanahan Paul, Russell Paul. The endogenous Mus81-Eme1 complex resolves Holliday junctions by a nick and counternick mechanism. Mol Cell. 2003 Sep;12(3):747–759. doi: 10.1016/s1097-2765(03)00342-3. [DOI] [PubMed] [Google Scholar]
  20. Goffeau A., Barrell B. G., Bussey H., Davis R. W., Dujon B., Feldmann H., Galibert F., Hoheisel J. D., Jacq C., Johnston M. Life with 6000 genes. Science. 1996 Oct 25;274(5287):546, 563-7. doi: 10.1126/science.274.5287.546. [DOI] [PubMed] [Google Scholar]
  21. Grishchuk A. L., Kohli J. Five RecA-like proteins of Schizosaccharomyces pombe are involved in meiotic recombination. Genetics. 2003 Nov;165(3):1031–1043. doi: 10.1093/genetics/165.3.1031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Haber J. E. The many interfaces of Mre11. Cell. 1998 Nov 25;95(5):583–586. doi: 10.1016/s0092-8674(00)81626-8. [DOI] [PubMed] [Google Scholar]
  23. Hartsuiker E., Vaessen E., Carr A. M., Kohli J. Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair. EMBO J. 2001 Dec 3;20(23):6660–6671. doi: 10.1093/emboj/20.23.6660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Horie S., Watanabe Y., Tanaka K., Nishiwaki S., Fujioka H., Abe H., Yamamoto M., Shimoda C. The Schizosaccharomyces pombe mei4+ gene encodes a meiosis-specific transcription factor containing a forkhead DNA-binding domain. Mol Cell Biol. 1998 Apr;18(4):2118–2129. doi: 10.1128/mcb.18.4.2118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Interthal H., Heyer W. D. 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. 2000 Jun;263(5):812–827. doi: 10.1007/s004380000241. [DOI] [PubMed] [Google Scholar]
  26. Keeney S., Giroux C. N., Kleckner N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell. 1997 Feb 7;88(3):375–384. doi: 10.1016/s0092-8674(00)81876-0. [DOI] [PubMed] [Google Scholar]
  27. Keeney S. Mechanism and control of meiotic recombination initiation. Curr Top Dev Biol. 2001;52:1–53. doi: 10.1016/s0070-2153(01)52008-6. [DOI] [PubMed] [Google Scholar]
  28. Kohli J., Bähler J. Homologous recombination in fission yeast: absence of crossover interference and synaptonemal complex. Experientia. 1994 Mar 15;50(3):295–306. doi: 10.1007/BF01924013. [DOI] [PubMed] [Google Scholar]
  29. Lin Y., Smith G. R. Transient, meiosis-induced expression of the rec6 and rec12 genes of Schizosaccharomyces pombe. Genetics. 1994 Mar;136(3):769–779. doi: 10.1093/genetics/136.3.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Mahadevaiah S. K., Turner J. M., Baudat F., Rogakou E. P., de Boer P., Blanco-Rodríguez J., Jasin M., Keeney S., Bonner W. M., Burgoyne P. S. Recombinational DNA double-strand breaks in mice precede synapsis. Nat Genet. 2001 Mar;27(3):271–276. doi: 10.1038/85830. [DOI] [PubMed] [Google Scholar]
  31. Manolis K. G., Nimmo E. R., Hartsuiker E., Carr A. M., Jeggo P. A., Allshire R. C. Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. EMBO J. 2001 Jan 15;20(1-2):210–221. doi: 10.1093/emboj/20.1.210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mata Juan, Lyne Rachel, Burns Gavin, Bähler Jürg. The transcriptional program of meiosis and sporulation in fission yeast. Nat Genet. 2002 Aug 5;32(1):143–147. doi: 10.1038/ng951. [DOI] [PubMed] [Google Scholar]
  33. Muris D. F., Vreeken K., Carr A. M., Broughton B. C., Lehmann A. R., Lohman P. H., Pastink A. Cloning the RAD51 homologue of Schizosaccharomyces pombe. Nucleic Acids Res. 1993 Sep 25;21(19):4586–4591. doi: 10.1093/nar/21.19.4586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nicklas R. B. How cells get the right chromosomes. Science. 1997 Jan 31;275(5300):632–637. doi: 10.1126/science.275.5300.632. [DOI] [PubMed] [Google Scholar]
  35. Osman Fekret, Dixon Julie, Doe Claudette L., Whitby Matthew C. Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Mol Cell. 2003 Sep;12(3):761–774. doi: 10.1016/s1097-2765(03)00343-5. [DOI] [PubMed] [Google Scholar]
  36. Ostermann K., Lorentz A., Schmidt H. The fission yeast rad22 gene, having a function in mating-type switching and repair of DNA damages, encodes a protein homolog to Rad52 of Saccharomyces cerevisiae. Nucleic Acids Res. 1993 Dec 25;21(25):5940–5944. doi: 10.1093/nar/21.25.5940. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ponticelli A. S., Smith G. R. Meiotic recombination-deficient mutants of Schizosaccharomyces pombe. Genetics. 1989 Sep;123(1):45–54. doi: 10.1093/genetics/123.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Pâques F., Haber J. E. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1999 Jun;63(2):349–404. doi: 10.1128/mmbr.63.2.349-404.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rockmill B., Sym M., Scherthan H., Roeder G. S. Roles for two RecA homologs in promoting meiotic chromosome synapsis. Genes Dev. 1995 Nov 1;9(21):2684–2695. doi: 10.1101/gad.9.21.2684. [DOI] [PubMed] [Google Scholar]
  40. Roeder G. S. Meiotic chromosomes: it takes two to tango. Genes Dev. 1997 Oct 15;11(20):2600–2621. doi: 10.1101/gad.11.20.2600. [DOI] [PubMed] [Google Scholar]
  41. Rogakou E. P., Pilch D. R., Orr A. H., Ivanova V. S., Bonner W. M. DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 1998 Mar 6;273(10):5858–5868. doi: 10.1074/jbc.273.10.5858. [DOI] [PubMed] [Google Scholar]
  42. Schmidt H. Effective long range mapping in Schizosaccharomyces pombe with the help of swi5. Curr Genet. 1993 Sep;24(3):271–273. doi: 10.1007/BF00351803. [DOI] [PubMed] [Google Scholar]
  43. Schwacha A., Kleckner N. Identification of double Holliday junctions as intermediates in meiotic recombination. Cell. 1995 Dec 1;83(5):783–791. doi: 10.1016/0092-8674(95)90191-4. [DOI] [PubMed] [Google Scholar]
  44. Schwacha A., Kleckner N. Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. Cell. 1994 Jan 14;76(1):51–63. doi: 10.1016/0092-8674(94)90172-4. [DOI] [PubMed] [Google Scholar]
  45. Shimada Midori, Nabeshima Kentaro, Tougan Takahiro, Nojima Hiroshi. The meiotic recombination checkpoint is regulated by checkpoint rad+ genes in fission yeast. EMBO J. 2002 Jun 3;21(11):2807–2818. doi: 10.1093/emboj/21.11.2807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shinohara A., Ogawa H., Matsuda Y., Ushio N., Ikeo K., Ogawa T. Cloning of human, mouse and fission yeast recombination genes homologous to RAD51 and recA. Nat Genet. 1993 Jul;4(3):239–243. doi: 10.1038/ng0793-239. [DOI] [PubMed] [Google Scholar]
  47. Shinohara A., Ogawa H., Ogawa T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell. 1992 May 1;69(3):457–470. doi: 10.1016/0092-8674(92)90447-k. [DOI] [PubMed] [Google Scholar]
  48. Smith Gerald R., Boddy Michael N., Shanahan Paul, Russell Paul. Fission yeast Mus81.Eme1 Holliday junction resolvase is required for meiotic crossing over but not for gene conversion. Genetics. 2003 Dec;165(4):2289–2293. doi: 10.1093/genetics/165.4.2289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Soustelle Christine, Vedel Michèle, Kolodner Richard, Nicolas Alain. Replication protein A is required for meiotic recombination in Saccharomyces cerevisiae. Genetics. 2002 Jun;161(2):535–547. doi: 10.1093/genetics/161.2.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Styrkársdóttir U., Egel R., Nielsen O. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion. Curr Genet. 1993 Feb;23(2):184–186. doi: 10.1007/BF00352020. [DOI] [PubMed] [Google Scholar]
  51. Sun H., Treco D., Schultes N. P., Szostak J. W. Double-strand breaks at an initiation site for meiotic gene conversion. Nature. 1989 Mar 2;338(6210):87–90. doi: 10.1038/338087a0. [DOI] [PubMed] [Google Scholar]
  52. Sung P., Trujillo K. M., Van Komen S. Recombination factors of Saccharomyces cerevisiae. Mutat Res. 2000 Jun 30;451(1-2):257–275. doi: 10.1016/s0027-5107(00)00054-3. [DOI] [PubMed] [Google Scholar]
  53. Tavassoli M., Shayeghi M., Nasim A., Watts F. Z. Cloning and characterisation of the Schizosaccharomyces pombe rad32 gene: a gene required for repair of double strand breaks and recombination. Nucleic Acids Res. 1995 Feb 11;23(3):383–388. doi: 10.1093/nar/23.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Uemura T., Yanagida M. Isolation of type I and II DNA topoisomerase mutants from fission yeast: single and double mutants show different phenotypes in cell growth and chromatin organization. EMBO J. 1984 Aug;3(8):1737–1744. doi: 10.1002/j.1460-2075.1984.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Ueno Masaru, Nakazaki Tomofumi, Akamatsu Yufuko, Watanabe Kikuo, Tomita Kazunori, Lindsay Howard D., Shinagawa Hideo, Iwasaki Hiroshi. Molecular characterization of the Schizosaccharomyces pombe nbs1+ gene involved in DNA repair and telomere maintenance. Mol Cell Biol. 2003 Sep;23(18):6553–6563. doi: 10.1128/MCB.23.18.6553-6563.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Wood V., Gwilliam R., Rajandream M-A, Lyne M., Lyne R., Stewart A., Sgouros J., Peat N., Hayles J., Baker S. The genome sequence of Schizosaccharomyces pombe. Nature. 2002 Feb 21;415(6874):871–880. doi: 10.1038/nature724. [DOI] [PubMed] [Google Scholar]
  57. Xu L., Ajimura M., Padmore R., Klein C., Kleckner N. NDT80, a meiosis-specific gene required for exit from pachytene in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Dec;15(12):6572–6581. doi: 10.1128/mcb.15.12.6572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Young Jennifer A., Schreckhise Randall W., Steiner Walter W., Smith Gerald R. Meiotic recombination remote from prominent DNA break sites in S. pombe. Mol Cell. 2002 Feb;9(2):253–263. doi: 10.1016/s1097-2765(02)00452-5. [DOI] [PubMed] [Google Scholar]
  59. Zenvirth D., Simchen G. Meiotic double-strand breaks in Schizosaccharomyces pombe. Curr Genet. 2000 Jul;38(1):33–38. doi: 10.1007/s002940000126. [DOI] [PubMed] [Google Scholar]
  60. de los Santos Teresa, Hunter Neil, Lee Cindy, Larkin Brittany, Loidl Josef, Hollingsworth Nancy M. The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics. 2003 May;164(1):81–94. doi: 10.1093/genetics/164.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. van den Bosch M, Vreeken K., Zonneveld J. B., Brandsma J. A., Lombaerts M., Murray J. M., Lohman P. H., Pastink A. Characterization of RAD52 homologs in the fission yeast Schizosaccharomyces pombe. Mutat Res. 2001 Jan 5;461(4):311–323. doi: 10.1016/s0921-8777(00)00060-4. [DOI] [PubMed] [Google Scholar]
  62. van den Bosch Michael, Zonneveld José B. M., Vreeken Kees, de Vries Femke A. T., Lohman Paul H. M., Pastink Albert. Differential expression and requirements for Schizosaccharomyces pombe RAD52 homologs in DNA repair and recombination. Nucleic Acids Res. 2002 Mar 15;30(6):1316–1324. doi: 10.1093/nar/30.6.1316. [DOI] [PMC free article] [PubMed] [Google Scholar]

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