Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 1995 Sep;141(1):75–86. doi: 10.1093/genetics/141.1.75

Heteroduplex DNA Formation and Homolog Pairing in Yeast Meiotic Mutants

D K Nag 1, H Scherthan 1, B Rockmill 1, J Bhargava 1, G S Roeder 1
PMCID: PMC1206742  PMID: 8536992

Abstract

Previous studies of Saccharomyces cerevisiae have identified several meiosis-specific genes whose products are required for wild-type levels of meiotic recombination and for normal synaptonemal complex (SC) formation. Several of these mutants were examined in a physical assay designed to detect heteroduplex DNA (hDNA) intermediates in meiotic recombination. hDNA was not detected in the rec102, mei4 and hop1 mutants; it was observed at reduced levels in red1, mek1 and mer1 strains and at greater than the wild-type level in zip1. These results indicate that the REC102, MEI4, HOP1, RED1, MEK1 and MER1 gene products act before hDNA formation in the meiotic recombination pathway, whereas ZIP1 acts later. The same mutants assayed for hDNA formation were monitored for meiotic chromosome pairing by in situ hybridization of chromosome-specific DNA probes to spread meiotic nuclei. Homolog pairing occurs at wild-type levels in the zip1 and mek1 mutants, but is substantially reduced in mei4, rec102, hop1, red1 and mer1 strains. Even mutants that fail to recombine or to make any SC or sc precursors undergo a significant amount of meiotic chromosome pairing. The in situ hybridization procedure revealed defects in meiotic chromatin condensation in mer1, red1 and hop1 strains.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. Burns N., Grimwade B., Ross-Macdonald P. B., Choi E. Y., Finberg K., Roeder G. S., Snyder M. Large-scale analysis of gene expression, protein localization, and gene disruption in Saccharomyces cerevisiae. Genes Dev. 1994 May 1;8(9):1087–1105. doi: 10.1101/gad.8.9.1087. [DOI] [PubMed] [Google Scholar]
  6. Bähler J., Wyler T., Loidl J., Kohli J. Unusual nuclear structures in meiotic prophase of fission yeast: a cytological analysis. J Cell Biol. 1993 Apr;121(2):241–256. doi: 10.1083/jcb.121.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Collins I., Newlon C. S. Meiosis-specific formation of joint DNA molecules containing sequences from homologous chromosomes. Cell. 1994 Jan 14;76(1):65–75. doi: 10.1016/0092-8674(94)90173-2. [DOI] [PubMed] [Google Scholar]
  9. Cool M., Malone R. E. Molecular and genetic analysis of the yeast early meiotic recombination genes REC102 and REC107/MER2. Mol Cell Biol. 1992 Mar;12(3):1248–1256. doi: 10.1128/mcb.12.3.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dresser M. E., Giroux C. N. Meiotic chromosome behavior in spread preparations of yeast. J Cell Biol. 1988 Mar;106(3):567–573. doi: 10.1083/jcb.106.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Engebrecht J. A., Voelkel-Meiman K., Roeder G. S. Meiosis-specific RNA splicing in yeast. Cell. 1991 Sep 20;66(6):1257–1268. doi: 10.1016/0092-8674(91)90047-3. [DOI] [PubMed] [Google Scholar]
  12. Engebrecht J., Roeder G. S. MER1, a yeast gene required for chromosome pairing and genetic recombination, is induced in meiosis. Mol Cell Biol. 1990 May;10(5):2379–2389. doi: 10.1128/mcb.10.5.2379. [DOI] [PMC free article] [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 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]
  15. Friedman D. B., Hollingsworth N. M., Byers B. Insertional mutations in the yeast HOP1 gene: evidence for multimeric assembly in meiosis. Genetics. 1994 Feb;136(2):449–464. doi: 10.1093/genetics/136.2.449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Game J. C., Sitney K. C., Cook V. E., Mortimer R. K. Use of a ring chromosome and pulsed-field gels to study interhomolog recombination, double-strand DNA breaks and sister-chromatid exchange in yeast. Genetics. 1989 Dec;123(4):695–713. doi: 10.1093/genetics/123.4.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Hollingsworth N. M., Johnson A. D. A conditional allele of the Saccharomyces cerevisiae HOP1 gene is suppressed by overexpression of two other meiosis-specific genes: RED1 and REC104. Genetics. 1993 Apr;133(4):785–797. doi: 10.1093/genetics/133.4.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hugerat Y., Simchen G. Mixed segregation and recombination of chromosomes and YACs during single-division meiosis in spo13 strains of Saccharomyces cerevisiae. Genetics. 1993 Oct;135(2):297–308. doi: 10.1093/genetics/135.2.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ivanov E. L., Korolev V. G., Fabre F. XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination. Genetics. 1992 Nov;132(3):651–664. doi: 10.1093/genetics/132.3.651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Kleckner N., Weiner B. M. Potential advantages of unstable interactions for pairing of chromosomes in meiotic, somatic, and premeiotic cells. Cold Spring Harb Symp Quant Biol. 1993;58:553–565. doi: 10.1101/sqb.1993.058.01.062. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Loidl J., Nairz K., Klein F. Meiotic chromosome synapsis in a haploid yeast. Chromosoma. 1991 May;100(4):221–228. doi: 10.1007/BF00344155. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Menees T. M., Roeder G. S. MEI4, a yeast gene required for meiotic recombination. Genetics. 1989 Dec;123(4):675–682. doi: 10.1093/genetics/123.4.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Menees T. M., Ross-MacDonald P. B., Roeder G. S. MEI4, a meiosis-specific yeast gene required for chromosome synapsis. Mol Cell Biol. 1992 Mar;12(3):1340–1351. doi: 10.1128/mcb.12.3.1340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Møens P. B., Pearlman R. E. Chromatin organization at meiosis. Bioessays. 1988 Nov;9(5):151–153. doi: 10.1002/bies.950090503. [DOI] [PubMed] [Google Scholar]
  32. Nag D. K., Petes T. D. Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2324–2331. doi: 10.1128/mcb.13.4.2324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Nag D. K., White M. A., Petes T. D. Palindromic sequences in heteroduplex DNA inhibit mismatch repair in yeast. Nature. 1989 Jul 27;340(6231):318–320. doi: 10.1038/340318a0. [DOI] [PubMed] [Google Scholar]
  34. Nandabalan K., Price L., Roeder G. S. Mutations in U1 snRNA bypass the requirement for a cell type-specific RNA splicing factor. Cell. 1993 Apr 23;73(2):407–415. doi: 10.1016/0092-8674(93)90239-m. [DOI] [PubMed] [Google Scholar]
  35. Nandabalan K., Roeder G. S. Binding of a cell-type-specific RNA splicing factor to its target regulatory sequence. Mol Cell Biol. 1995 Apr;15(4):1953–1960. doi: 10.1128/mcb.15.4.1953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Orr-Weaver T. L., Szostak J. W. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. doi: 10.1128/mr.49.1.33-58.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rockmill B., Engebrecht J. A., Scherthan H., Loidl J., Roeder G. S. The yeast MER2 gene is required for chromosome synapsis and the initiation of meiotic recombination. Genetics. 1995 Sep;141(1):49–59. doi: 10.1093/genetics/141.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. 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]
  40. 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]
  41. 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]
  42. 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]
  43. Sun H., Treco D., Szostak J. W. Extensive 3'-overhanging, single-stranded DNA associated with the meiosis-specific double-strand breaks at the ARG4 recombination initiation site. Cell. 1991 Mar 22;64(6):1155–1161. doi: 10.1016/0092-8674(91)90270-9. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Sym M., Roeder G. S. Zip1-induced changes in synaptonemal complex structure and polycomplex assembly. J Cell Biol. 1995 Feb;128(4):455–466. doi: 10.1083/jcb.128.4.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. 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]
  47. Wu T. C., Lichten M. Meiosis-induced double-strand break sites determined by yeast chromatin structure. Science. 1994 Jan 28;263(5146):515–518. doi: 10.1126/science.8290959. [DOI] [PubMed] [Google Scholar]
  48. Zenvirth D., Arbel T., Sherman A., Goldway M., Klein S., Simchen G. Multiple sites for double-strand breaks in whole meiotic chromosomes of Saccharomyces cerevisiae. EMBO J. 1992 Sep;11(9):3441–3447. doi: 10.1002/j.1460-2075.1992.tb05423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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