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Genetics. May 1994; 137(1): 19–39.
PMCID: PMC1205935

Interaction between Mismatch Repair and Genetic Recombination in Saccharomyces Cerevisiae

Abstract

The yeast Saccharomyces cerevisiae encodes a set of genes that show strong amino acid sequence similarity to MutS and MutL, proteins required for mismatch repair in Escherichia coli. We examined the role of MSH2 and PMS1, yeast homologs of mutS and mutL, respectively, in the repair of base pair mismatches formed during meiotic recombination. By using specifically marked HIS4 and ARG4 alleles, we showed that msh2 mutants displayed a severe defect in the repair of all base pair mismatches as well as 1-, 2- and 4-bp insertion/deletion mispairs. The msh2 and pms1 phenotypes were indistinguishable, suggesting that the wild-type gene products act in the same repair pathway. A comparison of gene conversion events in wild-type and msh2 mutants indicated that mismatch repair plays an important role in genetic recombination. (1) Tetrad analysis at five different loci revealed that, in msh2 mutants, the majority of aberrant segregants displayed a sectored phenotype, consistent with a failure to repair mismatches created during heteroduplex formation. In wild type, base pair mismatches were almost exclusively repaired toward conversion rather than restoration. (2) In msh2 strains 10-19% of the aberrant tetrads were Ab4:4. (3) Polarity gradients at HIS4 and ARG4 were nearly abolished in msh2 mutants. The frequency of gene conversion at the 3' end of these genes was increased and was nearly the frequency observed at the 5' end. (4) Co-conversion studies were consistent with mismatch repair acting to regulate heteroduplex DNA tract length. We favor a model proposing that recombination events occur through the formation and resolution of heteroduplex intermediates and that mismatch repair proteins specifically interact with recombination enzymes to regulate the length of symmetric heteroduplex DNA.

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Selected References

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  • Bailis AM, Rothstein R. A defect in mismatch repair in Saccharomyces cerevisiae stimulates ectopic recombination between homeologous genes by an excision repair dependent process. Genetics. 1990 Nov;126(3):535–547. [PMC free article] [PubMed]
  • Bishop DK, Kolodner RD. Repair of heteroduplex plasmid DNA after transformation into Saccharomyces cerevisiae. Mol Cell Biol. 1986 Oct;6(10):3401–3409. [PMC free article] [PubMed]
  • Bishop DK, Williamson MS, Fogel S, Kolodner RD. The role of heteroduplex correction in gene conversion in Saccharomyces cerevisiae. Nature. 1987 Jul 23;328(6128):362–364. [PubMed]
  • Bishop DK, Andersen J, Kolodner RD. Specificity of mismatch repair following transformation of Saccharomyces cerevisiae with heteroduplex plasmid DNA. Proc Natl Acad Sci U S A. 1989 May;86(10):3713–3717. [PMC free article] [PubMed]
  • Cullin C, Pompon D. Synthesis of functional mouse cytochromes P-450 P1 and chimeric P-450 P3-1 in the yeast Saccharomyces cerevisiae. Gene. 1988 May 30;65(2):203–217. [PubMed]
  • Detloff P, Petes TD. Measurements of excision repair tracts formed during meiotic recombination in Saccharomyces cerevisiae. Mol Cell Biol. 1992 Apr;12(4):1805–1814. [PMC free article] [PubMed]
  • Detloff P, Sieber J, Petes TD. Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1991 Feb;11(2):737–745. [PMC free article] [PubMed]
  • Detloff P, White MA, Petes TD. Analysis of a gene conversion gradient at the HIS4 locus in Saccharomyces cerevisiae. Genetics. 1992 Sep;132(1):113–123. [PMC free article] [PubMed]
  • Feinberg AP, Vogelstein B. "A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity". Addendum. Anal Biochem. 1984 Feb;137(1):266–267. [PubMed]
  • Gietz RD, Schiestl RH. Applications of high efficiency lithium acetate transformation of intact yeast cells using single-stranded nucleic acids as carrier. Yeast. 1991 Apr;7(3):253–263. [PubMed]
  • Haber JE, Ray BL, Kolb JM, White CI. Rapid kinetics of mismatch repair of heteroduplex DNA that is formed during recombination in yeast. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3363–3367. [PMC free article] [PubMed]
  • Holmes J, Jr, Clark S, Modrich P. Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines. Proc Natl Acad Sci U S A. 1990 Aug;87(15):5837–5841. [PMC free article] [PubMed]
  • Kane SM, Roth R. Carbohydrate metabolism during ascospore development in yeast. J Bacteriol. 1974 Apr;118(1):8–14. [PMC free article] [PubMed]
  • Kolodkin AL, Klar AJ, Stahl FW. Double-strand breaks can initiate meiotic recombination in S. cerevisiae. Cell. 1986 Aug 29;46(5):733–740. [PubMed]
  • Kramer B, Kramer W, Williamson MS, Fogel S. Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes. Mol Cell Biol. 1989 Oct;9(10):4432–4440. [PMC free article] [PubMed]
  • Kramer W, Kramer B, Williamson MS, Fogel S. Cloning and nucleotide sequence of DNA mismatch repair gene PMS1 from Saccharomyces cerevisiae: homology of PMS1 to procaryotic MutL and HexB. J Bacteriol. 1989 Oct;171(10):5339–5346. [PMC free article] [PubMed]
  • Lichten M, Borts RH, Haber JE. Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics. 1987 Feb;115(2):233–246. [PMC free article] [PubMed]
  • Lichten M, Goyon C, Schultes NP, Treco D, Szostak JW, Haber JE, Nicolas A. Detection of heteroduplex DNA molecules among the products of Saccharomyces cerevisiae meiosis. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7653–7657. [PMC free article] [PubMed]
  • Meselson MS, Radding CM. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. [PMC free article] [PubMed]
  • 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. [PubMed]
  • Modrich P. Mechanisms and biological effects of mismatch repair. Annu Rev Genet. 1991;25:229–253. [PubMed]
  • Nag DK, Petes TD. Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2324–2331. [PMC free article] [PubMed]
  • Nicolas A, Treco D, Schultes NP, Szostak JW. An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae. Nature. 1989 Mar 2;338(6210):35–39. [PubMed]
  • Orr-Weaver TL, Szostak JW. Fungal recombination. Microbiol Rev. 1985 Mar;49(1):33–58. [PMC free article] [PubMed]
  • Porter SE, White MA, Petes TD. Genetic evidence that the meiotic recombination hotspot at the HIS4 locus of Saccharomyces cerevisiae does not represent a site for a symmetrically processed double-strand break. Genetics. 1993 May;134(1):5–19. [PMC free article] [PubMed]
  • Radding CM. Homologous pairing and strand exchange in genetic recombination. Annu Rev Genet. 1982;16:405–437. [PubMed]
  • Reenan RA, Kolodner RD. Isolation and characterization of two Saccharomyces cerevisiae genes encoding homologs of the bacterial HexA and MutS mismatch repair proteins. Genetics. 1992 Dec;132(4):963–973. [PMC free article] [PubMed]
  • Reenan RA, Kolodner RD. Characterization of insertion mutations in the Saccharomyces cerevisiae MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear functions. Genetics. 1992 Dec;132(4):975–985. [PMC free article] [PubMed]
  • Resnick MA. The repair of double-strand breaks in DNA; a model involving recombination. J Theor Biol. 1976 Jun;59(1):97–106. [PubMed]
  • Resnick MA, Zgaga Z, Hieter P, Westmoreland J, Fogel S, Nilsson-Tillgren T. Recombinant repair of diverged DNAs: a study of homoeologous chromosomes and mammalian YACs in yeast. Mol Gen Genet. 1992 Jul;234(1):65–73. [PubMed]
  • Rocco V, de Massy B, Nicolas A. The Saccharomyces cerevisiae ARG4 initiator of meiotic gene conversion and its associated double-strand DNA breaks can be inhibited by transcriptional interference. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12068–12072. [PMC free article] [PubMed]
  • Rossignol JL, Nicolas A, Hamza H, Langin T. Origins of gene conversion and reciprocal exchange in Ascobolus. Cold Spring Harb Symp Quant Biol. 1984;49:13–21. [PubMed]
  • Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. [PubMed]
  • Strathern JN, Weinstock KG, Higgins DR, McGill CB. A novel recombinator in yeast based on gene II protein from bacteriophage f1. Genetics. 1991 Jan;127(1):61–73. [PMC free article] [PubMed]
  • Sun H, Treco D, Schultes NP, Szostak JW. Double-strand breaks at an initiation site for meiotic gene conversion. Nature. 1989 Mar 2;338(6210):87–90. [PubMed]
  • Sun H, Treco D, Szostak JW. 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. [PubMed]
  • Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. [PubMed]
  • Wheeler CJ, Maloney D, Fogel S, Goodenow RS. Microconversion between murine H-2 genes integrated into yeast. Nature. 1990 Sep 13;347(6289):192–194. [PubMed]
  • White JH, Lusnak K, Fogel S. Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate. Nature. 1985 May 23;315(6017):350–352. [PubMed]
  • White MA, Wierdl M, Detloff P, Petes TD. DNA-binding protein RAP1 stimulates meiotic recombination at the HIS4 locus in yeast. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9755–9759. [PMC free article] [PubMed]
  • Williamson MS, Game JC, Fogel S. Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of pms1-1 and pms1-2. Genetics. 1985 Aug;110(4):609–646. [PMC free article] [PubMed]

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