Skip to main content
Genetics logoLink to Genetics
. 1999 Apr;151(4):1299–1313. doi: 10.1093/genetics/151.4.1299

The role of the mismatch repair machinery in regulating mitotic and meiotic recombination between diverged sequences in yeast.

W Chen 1, S Jinks-Robertson 1
PMCID: PMC1460550  PMID: 10101158

Abstract

Nonidentical recombination substrates recombine less efficiently than do identical substrates in yeast, and much of this inhibition can be attributed to action of the mismatch repair (MMR) machinery. In this study an intron-based inverted repeat assay system has been used to directly compare the rates of mitotic and meiotic recombination between pairs of 350-bp substrates varying from 82% to 100% in sequence identity. The recombination rate data indicate that sequence divergence impacts mitotic and meiotic recombination similarly, although subtle differences are evident. In addition to assessing recombination rates as a function of sequence divergence, the endpoints of mitotic and meiotic recombination events involving 94%-identical substrates were determined by DNA sequencing. The endpoint analysis indicates that the extent of meiotic heteroduplex DNA formed in a MMR-defective strain is 65% longer than that formed in a wild-type strain. These data are consistent with a model in which the MMR machinery interferes with the formation and/or extension of heteroduplex intermediates during recombination.

Full Text

The Full Text of this article is available as a PDF (215.0 KB).

Selected References

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

  1. Ahn B. Y., Livingston D. M. Mitotic gene conversion lengths, coconversion patterns, and the incidence of reciprocal recombination in a Saccharomyces cerevisiae plasmid system. Mol Cell Biol. 1986 Nov;6(11):3685–3693. doi: 10.1128/mcb.6.11.3685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alani E., Reenan R. A., Kolodner R. D. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics. 1994 May;137(1):19–39. doi: 10.1093/genetics/137.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
  4. Borts R. H., Haber J. E. Length and distribution of meiotic gene conversion tracts and crossovers in Saccharomyces cerevisiae. Genetics. 1989 Sep;123(1):69–80. doi: 10.1093/genetics/123.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borts R. H., Leung W. Y., Kramer W., Kramer B., Williamson M., Fogel S., Haber J. E. Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics. 1990 Mar;124(3):573–584. doi: 10.1093/genetics/124.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chambers S. R., Hunter N., Louis E. J., Borts R. H. The mismatch repair system reduces meiotic homeologous recombination and stimulates recombination-dependent chromosome loss. Mol Cell Biol. 1996 Nov;16(11):6110–6120. doi: 10.1128/mcb.16.11.6110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen W., Jinks-Robertson S. Mismatch repair proteins regulate heteroduplex formation during mitotic recombination in yeast. Mol Cell Biol. 1998 Nov;18(11):6525–6537. doi: 10.1128/mcb.18.11.6525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Claverys J. P., Lacks S. A. Heteroduplex deoxyribonucleic acid base mismatch repair in bacteria. Microbiol Rev. 1986 Jun;50(2):133–165. doi: 10.1128/mr.50.2.133-165.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Datta A., Adjiri A., New L., Crouse G. F., Jinks Robertson S. Mitotic crossovers between diverged sequences are regulated by mismatch repair proteins in Saccaromyces cerevisiae. Mol Cell Biol. 1996 Mar;16(3):1085–1093. doi: 10.1128/mcb.16.3.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Datta A., Hendrix M., Lipsitch M., Jinks-Robertson S. Dual roles for DNA sequence identity and the mismatch repair system in the regulation of mitotic crossing-over in yeast. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9757–9762. doi: 10.1073/pnas.94.18.9757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Davidow L. S., Byers B. Enhanced gene conversion and postmeiotic segregation in pachytene-arrested Saccharomyces cerevisiae. Genetics. 1984 Feb;106(2):165–183. doi: 10.1093/genetics/106.2.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fabre F., Boulet A., Roman H. Gene conversion at different points in the mitotic cycle of Saccharomyces cerevisiae. Mol Gen Genet. 1984;195(1-2):139–143. doi: 10.1007/BF00332736. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Haber J. E., Thorburn P. C., Rogers D. Meiotic and mitotic behavior of dicentric chromosomes in Saccharomyces cerevisiae. Genetics. 1984 Feb;106(2):185–205. doi: 10.1093/genetics/106.2.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Habraken Y., Sung P., Prakash L., Prakash S. Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-PMS1 complex. Curr Biol. 1997 Oct 1;7(10):790–793. doi: 10.1016/s0960-9822(06)00337-x. [DOI] [PubMed] [Google Scholar]
  16. Harris S., Rudnicki K. S., Haber J. E. Gene conversions and crossing over during homologous and homeologous ectopic recombination in Saccharomyces cerevisiae. Genetics. 1993 Sep;135(1):5–16. doi: 10.1093/genetics/135.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  18. Hunter N., Chambers S. R., Louis E. J., Borts R. H. The mismatch repair system contributes to meiotic sterility in an interspecific yeast hybrid. EMBO J. 1996 Apr 1;15(7):1726–1733. [PMC free article] [PubMed] [Google Scholar]
  19. Jinks-Robertson S., Michelitch M., Ramcharan S. Substrate length requirements for efficient mitotic recombination in Saccharomyces cerevisiae. Mol Cell Biol. 1993 Jul;13(7):3937–3950. doi: 10.1128/mcb.13.7.3937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson R. E., Kovvali G. K., Guzder S. N., Amin N. S., Holm C., Habraken Y., Sung P., Prakash L., Prakash S. Evidence for involvement of yeast proliferating cell nuclear antigen in DNA mismatch repair. J Biol Chem. 1996 Nov 8;271(45):27987–27990. doi: 10.1074/jbc.271.45.27987. [DOI] [PubMed] [Google Scholar]
  21. Judd S. R., Petes T. D. Physical lengths of meiotic and mitotic gene conversion tracts in Saccharomyces cerevisiae. Genetics. 1988 Mar;118(3):401–410. doi: 10.1093/genetics/118.3.401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kadyk L. C., Hartwell L. H. Sister chromatids are preferred over homologs as substrates for recombinational repair in Saccharomyces cerevisiae. Genetics. 1992 Oct;132(2):387–402. doi: 10.1093/genetics/132.2.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Kolodner R. Biochemistry and genetics of eukaryotic mismatch repair. Genes Dev. 1996 Jun 15;10(12):1433–1442. doi: 10.1101/gad.10.12.1433. [DOI] [PubMed] [Google Scholar]
  25. Modrich P., Lahue R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem. 1996;65:101–133. doi: 10.1146/annurev.bi.65.070196.000533. [DOI] [PubMed] [Google Scholar]
  26. Mézard C., Pompon D., Nicolas A. Recombination between similar but not identical DNA sequences during yeast transformation occurs within short stretches of identity. Cell. 1992 Aug 21;70(4):659–670. doi: 10.1016/0092-8674(92)90434-e. [DOI] [PubMed] [Google Scholar]
  27. Porter G., Westmoreland J., Priebe S., Resnick M. A. Homologous and homeologous intermolecular gene conversion are not differentially affected by mutations in the DNA damage or the mismatch repair genes RAD1, RAD50, RAD51, RAD52, RAD54, PMS1 and MSH2. Genetics. 1996 Jun;143(2):755–767. doi: 10.1093/genetics/143.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rayssiguier C., Thaler D. S., Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989 Nov 23;342(6248):396–401. doi: 10.1038/342396a0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Schwacha A., Kleckner N. Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway. Cell. 1997 Sep 19;90(6):1123–1135. doi: 10.1016/s0092-8674(00)80378-5. [DOI] [PubMed] [Google Scholar]
  31. Selva E. M., Maderazo A. B., Lahue R. S. Differential effects of the mismatch repair genes MSH2 and MSH3 on homeologous recombination in Saccharomyces cerevisiae. Mol Gen Genet. 1997 Dec;257(1):71–82. doi: 10.1007/pl00008619. [DOI] [PubMed] [Google Scholar]
  32. Selva E. M., New L., Crouse G. F., Lahue R. S. Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Genetics. 1995 Mar;139(3):1175–1188. doi: 10.1093/genetics/139.3.1175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shen P., Huang H. V. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics. 1986 Mar;112(3):441–457. doi: 10.1093/genetics/112.3.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sweetser D. B., Hough H., Whelden J. F., Arbuckle M., Nickoloff J. A. Fine-resolution mapping of spontaneous and double-strand break-induced gene conversion tracts in Saccharomyces cerevisiae reveals reversible mitotic conversion polarity. Mol Cell Biol. 1994 Jun;14(6):3863–3875. doi: 10.1128/mcb.14.6.3863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Symington L. S., Petes T. D. Expansions and contractions of the genetic map relative to the physical map of yeast chromosome III. Mol Cell Biol. 1988 Feb;8(2):595–604. doi: 10.1128/mcb.8.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Umar A., Buermeyer A. B., Simon J. A., Thomas D. C., Clark A. B., Liskay R. M., Kunkel T. A. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell. 1996 Oct 4;87(1):65–73. doi: 10.1016/s0092-8674(00)81323-9. [DOI] [PubMed] [Google Scholar]
  38. Vulić M., Dionisio F., Taddei F., Radman M. Molecular keys to speciation: DNA polymorphism and the control of genetic exchange in enterobacteria. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9763–9767. doi: 10.1073/pnas.94.18.9763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Worth L., Jr, Clark S., Radman M., Modrich P. Mismatch repair proteins MutS and MutL inhibit RecA-catalyzed strand transfer between diverged DNAs. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3238–3241. doi: 10.1073/pnas.91.8.3238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Zahrt T. C., Maloy S. Barriers to recombination between closely related bacteria: MutS and RecBCD inhibit recombination between Salmonella typhimurium and Salmonella typhi. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9786–9791. doi: 10.1073/pnas.94.18.9786. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zawadzki P., Roberts M. S., Cohan F. M. The log-linear relationship between sexual isolation and sequence divergence in Bacillus transformation is robust. Genetics. 1995 Jul;140(3):917–932. doi: 10.1093/genetics/140.3.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. de Wind N., Dekker M., Berns A., Radman M., te Riele H. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell. 1995 Jul 28;82(2):321–330. doi: 10.1016/0092-8674(95)90319-4. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES