Skip to main content
Genetics logoLink to Genetics
. 1998 Feb;148(2):581–598. doi: 10.1093/genetics/148.2.581

Yeast meiotic mutants proficient for the induction of ectopic recombination.

J Engebrecht 1, S Masse 1, L Davis 1, K Rose 1, T Kessel 1
PMCID: PMC1459833  PMID: 9504908

Abstract

A screen was designed to identify Saccharomyces cerevisiae mutants that were defective in meiosis yet proficient for meiotic ectopic recombination in the return-to-growth protocol. Seven mutants alleles were isolated; two are important for chromosome synapsis (RED1, MEK1) and five function independently of recombination (SPO14, GSG1, SPOT8/MUM2, 3, 4). Similar to the spoT8-1 mutant, mum2 deletion strains do not undergo premeiotic DNA synthesis, arrest prior to the first meiotic division and fail to sporulate. Surprisingly, although DNA replication does not occur, mum2 mutants are induced for high levels of ectopic recombination. gsg1 diploids are reduced in their ability to complete premeiotic DNA synthesis and the meiotic divisions, and a small percentage of cells produce spores. mum3 mutants sporulate poorly and the spores produced are inviable. Finally, mum4-1 mutants produce inviable spores. The meiotic/sporulation defects of gsg1, mum2, and mum3 are not relieved by spo11 or spo13 mutations, indicating that the mutant defects are not dependent on the initiation of recombination or completion of both meiotic divisions. In contrast, the spore inviability of the mum4-1 mutant is rescued by the spo13 mutation. The mum4-1 spo13 mutant undergoes a single, predominantly equational division, suggesting that MUM4 functions at or prior to the first meiotic division. Although recombination is variably affected in the gsg1 and mum mutants, we hypothesize that these mutants define genes important for aspects of meiosis not directly related to recombination.

Full Text

The Full Text of this article is available as a PDF (267.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ajimura M., Leem S. H., Ogawa H. Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics. 1993 Jan;133(1):51–66. doi: 10.1093/genetics/133.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alani E., Cao L., Kleckner N. A method for gene disruption that allows repeated use of URA3 selection in the construction of multiply disrupted yeast strains. Genetics. 1987 Aug;116(4):541–545. doi: 10.1534/genetics.112.541.test. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhargava J., Engebrecht J., Roeder G. S. The rec102 mutant of yeast is defective in meiotic recombination and chromosome synapsis. Genetics. 1992 Jan;130(1):59–69. doi: 10.1093/genetics/130.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Borts R. H., Lichten M., Haber J. E. Analysis of meiosis-defective mutations in yeast by physical monitoring of recombination. Genetics. 1986 Jul;113(3):551–567. doi: 10.1093/genetics/113.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Callan H. G. Replication of DNA in the chromosomes of eukaryotes. Proc R Soc Lond B Biol Sci. 1972 Apr 18;181(1062):19–41. doi: 10.1098/rspb.1972.0039. [DOI] [PubMed] [Google Scholar]
  7. Chua P. R., Roeder G. S. Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference. Genes Dev. 1997 Jul 15;11(14):1786–1800. doi: 10.1101/gad.11.14.1786. [DOI] [PubMed] [Google Scholar]
  8. Collins I., Newlon C. S. Chromosomal DNA replication initiates at the same origins in meiosis and mitosis. Mol Cell Biol. 1994 May;14(5):3524–3534. doi: 10.1128/mcb.14.5.3524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Conrad M. N., Dominguez A. M., Dresser M. E. Ndj1p, a meiotic telomere protein required for normal chromosome synapsis and segregation in yeast. Science. 1997 May 23;276(5316):1252–1255. doi: 10.1126/science.276.5316.1252. [DOI] [PubMed] [Google Scholar]
  10. Dawes I. W., Hardie I. D. Selective killing of vegetative cells in sporulated yeast cultures by exposure to diethyl ether. Mol Gen Genet. 1974;131(4):281–289. doi: 10.1007/BF00264859. [DOI] [PubMed] [Google Scholar]
  11. Elledge S. J., Davis R. W. A family of versatile centromeric vectors designed for use in the sectoring-shuffle mutagenesis assay in Saccharomyces cerevisiae. Gene. 1988 Oct 30;70(2):303–312. doi: 10.1016/0378-1119(88)90202-8. [DOI] [PubMed] [Google Scholar]
  12. Engebrecht J., Hirsch J., Roeder G. S. Meiotic gene conversion and crossing over: their relationship to each other and to chromosome synapsis and segregation. Cell. 1990 Sep 7;62(5):927–937. doi: 10.1016/0092-8674(90)90267-i. [DOI] [PubMed] [Google Scholar]
  13. Engebrecht J., Roeder G. S. Yeast mer1 mutants display reduced levels of meiotic recombination. Genetics. 1989 Feb;121(2):237–247. doi: 10.1093/genetics/121.2.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Esposito M. S., Esposito R. E. Genes controlling meiosis and spore formation in yeast. Genetics. 1974 Sep;78(1):215–225. doi: 10.1093/genetics/78.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Esposito R. E., Esposito M. S. Genetic recombination and commitment to meiosis in Saccharomyces. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3172–3176. doi: 10.1073/pnas.71.8.3172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feldmann H., Aigle M., Aljinovic G., André B., Baclet M. C., Barthe C., Baur A., Bécam A. M., Biteau N., Boles E. Complete DNA sequence of yeast chromosome II. EMBO J. 1994 Dec 15;13(24):5795–5809. doi: 10.1002/j.1460-2075.1994.tb06923.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Fleig U. N., Pridmore R. D., Philippsen P. Construction of LYS2 cartridges for use in genetic manipulations of Saccharomyces cerevisiae. Gene. 1986;46(2-3):237–245. doi: 10.1016/0378-1119(86)90408-7. [DOI] [PubMed] [Google Scholar]
  18. Fogel S., Hurst D. D. Meiotic gene conversion in yeast tetrads and the theory of recombination. Genetics. 1967 Oct;57(2):455–481. doi: 10.1093/genetics/57.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Goldman A. S., Lichten M. The efficiency of meiotic recombination between dispersed sequences in Saccharomyces cerevisiae depends upon their chromosomal location. Genetics. 1996 Sep;144(1):43–55. doi: 10.1093/genetics/144.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Goyon C., Lichten M. Timing of molecular events in meiosis in Saccharomyces cerevisiae: stable heteroduplex DNA is formed late in meiotic prophase. Mol Cell Biol. 1993 Jan;13(1):373–382. doi: 10.1128/mcb.13.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haber J. E., Leung W. Y., Borts R. H., Lichten M. The frequency of meiotic recombination in yeast is independent of the number and position of homologous donor sequences: implications for chromosome pairing. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1120–1124. doi: 10.1073/pnas.88.4.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hill J. E., Myers A. M., Koerner T. J., Tzagoloff A. Yeast/E. coli shuttle vectors with multiple unique restriction sites. Yeast. 1986 Sep;2(3):163–167. doi: 10.1002/yea.320020304. [DOI] [PubMed] [Google Scholar]
  23. Hollingsworth N. M., Byers B. HOP1: a yeast meiotic pairing gene. Genetics. 1989 Mar;121(3):445–462. doi: 10.1093/genetics/121.3.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hollingsworth N. M., Goetsch L., Byers B. The HOP1 gene encodes a meiosis-specific component of yeast chromosomes. Cell. 1990 Apr 6;61(1):73–84. doi: 10.1016/0092-8674(90)90216-2. [DOI] [PubMed] [Google Scholar]
  25. Hollingsworth N. M., Ponte L. Genetic interactions between HOP1, RED1 and MEK1 suggest that MEK1 regulates assembly of axial element components during meiosis in the yeast Saccharomyces cerevisiae. Genetics. 1997 Sep;147(1):33–42. doi: 10.1093/genetics/147.1.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hollingsworth N. M., Ponte L., Halsey C. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 1995 Jul 15;9(14):1728–1739. doi: 10.1101/gad.9.14.1728. [DOI] [PubMed] [Google Scholar]
  27. Honigberg S. M., Conicella C., Espositio R. E. Commitment to meiosis in Saccharomyces cerevisiae: involvement of the SPO14 gene. Genetics. 1992 Apr;130(4):703–716. doi: 10.1093/genetics/130.4.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Jinks-Robertson S., Petes T. D. Chromosomal translocations generated by high-frequency meiotic recombination between repeated yeast genes. Genetics. 1986 Nov;114(3):731–752. doi: 10.1093/genetics/114.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Johnston L. H., Williamson D. H., Johnson A. L., Fennell D. J. On the mechanism of premeiotic DNA synthesis in the yeast Saccharomyces cerevisiae. Exp Cell Res. 1982 Sep;141(1):53–62. doi: 10.1016/0014-4827(82)90067-2. [DOI] [PubMed] [Google Scholar]
  31. Kaytor M. D., Livingston D. M. GSG1, a yeast gene required for sporulation. Yeast. 1995 Sep 30;11(12):1147–1155. doi: 10.1002/yea.320111205. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Klapholz S., Esposito R. E. Recombination and chromosome segregation during the single division meiosis in SPO12-1 and SPO13-1 diploids. Genetics. 1980 Nov;96(3):589–611. doi: 10.1093/genetics/96.3.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Klapholz S., Waddell C. S., Esposito R. E. The role of the SPO11 gene in meiotic recombination in yeast. Genetics. 1985 Jun;110(2):187–216. doi: 10.1093/genetics/110.2.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Kleckner N. Meiosis: how could it work? Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8167–8174. doi: 10.1073/pnas.93.16.8167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kobayashi T., Hotta Y., Tabata S. Isolation and characterization of a yeast gene that is homologous with a meiosis-specific cDNA from a plant. Mol Gen Genet. 1993 Feb;237(1-2):225–232. doi: 10.1007/BF00282804. [DOI] [PubMed] [Google Scholar]
  37. Kofman-Alfaro S., Chandley A. C. Meiosis in the male mouse. An autoradiographic investigation. Chromosoma. 1970;31(4):404–420. doi: 10.1007/BF00285832. [DOI] [PubMed] [Google Scholar]
  38. Leem S. H., Ogawa H. The MRE4 gene encodes a novel protein kinase homologue required for meiotic recombination in Saccharomyces cerevisiae. Nucleic Acids Res. 1992 Feb 11;20(3):449–457. doi: 10.1093/nar/20.3.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lichten M., Borts R. H., Haber J. E. Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics. 1987 Feb;115(2):233–246. doi: 10.1093/genetics/115.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Loidl J., Klein F., Scherthan H. Homologous pairing is reduced but not abolished in asynaptic mutants of yeast. J Cell Biol. 1994 Jun;125(6):1191–1200. doi: 10.1083/jcb.125.6.1191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Lydall D., Nikolsky Y., Bishop D. K., Weinert T. A meiotic recombination checkpoint controlled by mitotic checkpoint genes. Nature. 1996 Oct 31;383(6603):840–843. doi: 10.1038/383840a0. [DOI] [PubMed] [Google Scholar]
  42. Malone R. E., Bullard S., Hermiston M., Rieger R., Cool M., Galbraith A. Isolation of mutants defective in early steps of meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics. 1991 May;128(1):79–88. doi: 10.1093/genetics/128.1.79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. McCarroll R. M., Esposito R. E. SPO13 negatively regulates the progression of mitotic and meiotic nuclear division in Saccharomyces cerevisiae. Genetics. 1994 Sep;138(1):47–60. doi: 10.1093/genetics/138.1.47. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. McKee A. H., Kleckner N. A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2. Genetics. 1997 Jul;146(3):797–816. doi: 10.1093/genetics/146.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. McKee A. H., Kleckner N. Mutations in Saccharomyces cerevisiae that block meiotic prophase chromosome metabolism and confer cell cycle arrest at pachytene identify two new meiosis-specific genes SAE1 and SAE3. Genetics. 1997 Jul;146(3):817–834. doi: 10.1093/genetics/146.3.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Padmore R., Cao L., Kleckner N. Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae. Cell. 1991 Sep 20;66(6):1239–1256. doi: 10.1016/0092-8674(91)90046-2. [DOI] [PubMed] [Google Scholar]
  47. Prinz S., Amon A., Klein F. Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae. Genetics. 1997 Jul;146(3):781–795. doi: 10.1093/genetics/146.3.781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rockmill B., Roeder G. S. A meiosis-specific protein kinase homolog required for chromosome synapsis and recombination. Genes Dev. 1991 Dec;5(12B):2392–2404. doi: 10.1101/gad.5.12b.2392. [DOI] [PubMed] [Google Scholar]
  49. Rockmill B., Roeder G. S. Meiosis in asynaptic yeast. Genetics. 1990 Nov;126(3):563–574. doi: 10.1093/genetics/126.3.563. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Rockmill B., Roeder G. S. RED1: a yeast gene required for the segregation of chromosomes during the reductional division of meiosis. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6057–6061. doi: 10.1073/pnas.85.16.6057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Roeder G. S. Sex and the single cell: meiosis in yeast. Proc Natl Acad Sci U S A. 1995 Nov 7;92(23):10450–10456. doi: 10.1073/pnas.92.23.10450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Rose K., Rudge S. A., Frohman M. A., Morris A. J., Engebrecht J. Phospholipase D signaling is essential for meiosis. Proc Natl Acad Sci U S A. 1995 Dec 19;92(26):12151–12155. doi: 10.1073/pnas.92.26.12151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Rose M. D., Novick P., Thomas J. H., Botstein D., Fink G. R. A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. Gene. 1987;60(2-3):237–243. doi: 10.1016/0378-1119(87)90232-0. [DOI] [PubMed] [Google Scholar]
  54. Ross-Macdonald P., Roeder G. S. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell. 1994 Dec 16;79(6):1069–1080. doi: 10.1016/0092-8674(94)90037-x. [DOI] [PubMed] [Google Scholar]
  55. Roth R. Chromosome replication during meiosis: identification of gene functions required for premeiotic DNA synthesis. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3087–3091. doi: 10.1073/pnas.70.11.3087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. doi: 10.1016/0076-6879(91)94022-5. [DOI] [PubMed] [Google Scholar]
  57. Sazer S., Sherwood S. W. Mitochondrial growth and DNA synthesis occur in the absence of nuclear DNA replication in fission yeast. J Cell Sci. 1990 Nov;97(Pt 3):509–516. doi: 10.1242/jcs.97.3.509. [DOI] [PubMed] [Google Scholar]
  58. Seifert H. S., Chen E. Y., So M., Heffron F. Shuttle mutagenesis: a method of transposon mutagenesis for Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1986 Feb;83(3):735–739. doi: 10.1073/pnas.83.3.735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Smith A. V., Roeder G. S. The yeast Red1 protein localizes to the cores of meiotic chromosomes. J Cell Biol. 1997 Mar 10;136(5):957–967. doi: 10.1083/jcb.136.5.957. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  61. Steele D. F., Morris M. E., Jinks-Robertson S. Allelic and ectopic interactions in recombination-defective yeast strains. Genetics. 1991 Jan;127(1):53–60. doi: 10.1093/genetics/127.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sym M., Engebrecht J. A., Roeder G. S. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis. Cell. 1993 Feb 12;72(3):365–378. doi: 10.1016/0092-8674(93)90114-6. [DOI] [PubMed] [Google Scholar]
  63. Tsuboi M. The isolation and genetic analysis of sporulation-deficient mutants in Saccharomyces cerevisiae. Mol Gen Genet. 1983;191(1):17–21. doi: 10.1007/BF00330883. [DOI] [PubMed] [Google Scholar]
  64. Vershon A. K., Hollingsworth N. M., Johnson A. D. Meiotic induction of the yeast HOP1 gene is controlled by positive and negative regulatory sites. Mol Cell Biol. 1992 Sep;12(9):3706–3714. doi: 10.1128/mcb.12.9.3706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Weiner B. M., Kleckner N. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell. 1994 Jul 1;77(7):977–991. doi: 10.1016/0092-8674(94)90438-3. [DOI] [PubMed] [Google Scholar]
  66. Williamson D. H., Johnston L. H., Fennell D. J., Simchen G. The timing of the S phase and other nuclear events in yeast meiosis. Exp Cell Res. 1983 Apr 15;145(1):209–217. doi: 10.1016/s0014-4827(83)80022-6. [DOI] [PubMed] [Google Scholar]
  67. 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]
  68. von Wettstein D., Rasmussen S. W., Holm P. B. The synaptonemal complex in genetic segregation. Annu Rev Genet. 1984;18:331–413. doi: 10.1146/annurev.ge.18.120184.001555. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES