• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Nov 1996; 16(11): 6110–6120.
PMCID: PMC231614

The mismatch repair system reduces meiotic homeologous recombination and stimulates recombination-dependent chromosome loss.

Abstract

Efficient genetic recombination requires near-perfect homology between participating molecules. Sequence divergence reduces the frequency of recombination, a process that is dependent on the activity of the mismatch repair system. The effects of chromosomal divergence in diploids of Saccharomyces cerevisiae in which one copy of chromosome III is derived from a closely related species, Saccharomyces paradoxus, have been examined. Meiotic recombination between the diverged chromosomes is decreased by 25-fold. Spore viability is reduced with an observable increase in the number of tetrads with only two or three viable spores. Asci with only two viable spores are disomic for chromosome III, consistent with meiosis I nondisjunction of the homeologs. Asci with three viable spores are highly enriched for recombinants relative to tetrads with four viable spores. In 96% of the class with three viable spores, only one spore possesses a recombinant chromosome III, suggesting that the recombination process itself contributes to meiotic death. This phenomenon is dependent on the activities of the mismatch repair genes PMS1 and MSH2. A model of mismatch-stimulated chromosome loss is proposed to account for this observation. As expected, crossing over is increased in pms1 and msh2 mutants. Furthermore, genetic exchange in pms1 msh2 double mutants is affected to a greater extent than in either mutant alone, suggesting that the two proteins act independently to inhibit homeologous recombination. All mismatch repair-deficient strains exhibited reductions in the rate of chromosome III nondisjunction.

Full Text

The Full Text of this article is available as a PDF (678K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adjiri A, Chanet R, Mezard C, Fabre F. Sequence comparison of the ARG4 chromosomal regions from the two related yeasts, Saccharomyces cerevisiae and Saccharomyces douglasii. Yeast. 1994 Mar;10(3):309–317. [PubMed]
  • Alani E, Reenan RA, Kolodner RD. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics. 1994 May;137(1):19–39. [PMC free article] [PubMed]
  • Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EA, Yu J, Ashley T, Arnheim N, et al. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell. 1995 Jul 28;82(2):309–319. [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]
  • Boeke JD, LaCroute F, Fink GR. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. [PubMed]
  • Borts RH, Haber JE. Meiotic recombination in yeast: alteration by multiple heterozygosities. Science. 1987 Sep 18;237(4821):1459–1465. [PubMed]
  • Borts RH, Leung WY, Kramer W, Kramer B, Williamson M, Fogel S, Haber JE. Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics. 1990 Mar;124(3):573–584. [PMC free article] [PubMed]
  • Chattoo BB, Sherman F, Azubalis DA, Fjellstedt TA, Mehnert D, Ogur M. Selection of lys2 Mutants of the Yeast SACCHAROMYCES CEREVISIAE by the Utilization of alpha-AMINOADIPATE. Genetics. 1979 Sep;93(1):51–65. [PMC free article] [PubMed]
  • Conde J, Fink GR. A mutant of Saccharomyces cerevisiae defective for nuclear fusion. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3651–3655. [PMC free article] [PubMed]
  • Datta A, Adjiri A, New L, Crouse GF, 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. [PMC free article] [PubMed]
  • Dawson DS, Murray AW, Szostak JW. An alternative pathway for meiotic chromosome segregation in yeast. Science. 1986 Nov 7;234(4777):713–717. [PubMed]
  • 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. [PubMed]
  • Doutriaux MP, Wagner R, Radman M. Mismatch-stimulated killing. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2576–2578. [PMC free article] [PubMed]
  • Dutcher SK. Internuclear transfer of genetic information in kar1-1/KAR1 heterokaryons in Saccharomyces cerevisiae. Mol Cell Biol. 1981 Mar;1(3):245–253. [PMC free article] [PubMed]
  • Fishel R, Kolodner RD. Identification of mismatch repair genes and their role in the development of cancer. Curr Opin Genet Dev. 1995 Jun;5(3):382–395. [PubMed]
  • Fogel S, Mortimer R, Lusnak K, Tavares F. Meiotic gene conversion: a signal of the basic recombination event in yeast. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):1325–1341. [PubMed]
  • Gietz D, St Jean A, Woods RA, Schiestl RH. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992 Mar 25;20(6):1425–1425. [PMC free article] [PubMed]
  • GRELL RF. A new model for secondary nondisjunction: the role of distributive pairing. Genetics. 1962 Dec;47:1737–1754. [PMC free article] [PubMed]
  • Guacci V, Kaback DB. Distributive disjunction of authentic chromosomes in Saccharomyces cerevisiae. Genetics. 1991 Mar;127(3):475–488. [PMC free article] [PubMed]
  • Haber JE, Hearn M. Rad52-independent mitotic gene conversion in Saccharomyces cerevisiae frequently results in chromosomal loss. Genetics. 1985 Sep;111(1):7–22. [PMC free article] [PubMed]
  • Hansen J, Kielland-Brandt MC. Saccharomyces carlsbergensis contains two functional MET2 alleles similar to homologues from S. cerevisiae and S. monacensis. Gene. 1994 Mar 11;140(1):33–40. [PubMed]
  • Hawley RS, McKim KS, Arbel T. Meiotic segregation in Drosophila melanogaster females: molecules, mechanisms, and myths. Annu Rev Genet. 1993;27:281–317. [PubMed]
  • Hawthorne D, Philippsen P. Genetic and molecular analysis of hybrids in the genus Saccharomyces involving S. cerevisiae, S. uvarum and a new species, S. douglasii. Yeast. 1994 Oct;10(10):1285–1296. [PubMed]
  • Herbert CJ, Dujardin G, Labouesse M, Slonimski PP. Divergence of the mitochondrial leucyl tRNA synthetase genes in two closely related yeasts Saccharomyces cerevisiae and Saccharomyces douglasii: a paradigm of incipient evolution. Mol Gen Genet. 1988 Aug;213(2-3):297–309. [PubMed]
  • Hollingsworth NM, 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. [PubMed]
  • Hunter N, Chambers SR, Louis EJ, Borts RH. 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]
  • Jensen RE, Herskowitz I. Directionality and regulation of cassette substitution in yeast. Cold Spring Harb Symp Quant Biol. 1984;49:97–104. [PubMed]
  • Kaback DB. Meiotic segregation of circular plasmid-minichromosomes from intact chromosomes in Saccharomyces cerevisiae. Curr Genet. 1989 Jun;15(6):385–392. [PubMed]
  • Kmiec E, Kroeger P, Holliday R, Holloman W. Homologous pairing promoted by Ustilago RecI protein. Cold Spring Harb Symp Quant Biol. 1984;49:675–682. [PubMed]
  • Kobayashi I. Mechanisms for gene conversion and homologous recombination: the double-strand break repair model and the successive half crossing-over model. Adv Biophys. 1992;28:81–133. [PubMed]
  • Kobayashi I, Takahashi N. Double-stranded gap repair of DNA by gene conversion in Escherichia coli. Genetics. 1988 Aug;119(4):751–757. [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]
  • Kusano K, Sunohara Y, Takahashi N, Yoshikura H, Kobayashi I. DNA double-strand break repair: genetic determinants of flanking crossing-over. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1173–1177. [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]
  • Loidl J, Scherthan H, Kaback DB. Physical association between nonhomologous chromosomes precedes distributive disjunction in yeast. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):331–334. [PMC free article] [PubMed]
  • Louis EJ, Haber JE. Nonrecombinant meiosis I nondisjunction in Saccharomyces cerevisiae induced by tRNA ochre suppressors. Genetics. 1989 Sep;123(1):81–95. [PMC free article] [PubMed]
  • Mann C, Davis RW. Meiotic disjunction of circular minichromosomes in yeast does not require DNA homology. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6017–6019. [PMC free article] [PubMed]
  • Marsischky GT, Filosi N, Kane MF, Kolodner R. Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair. Genes Dev. 1996 Feb 15;10(4):407–420. [PubMed]
  • Matic I, Rayssiguier C, Radman M. Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell. 1995 Feb 10;80(3):507–515. [PubMed]
  • McCusker JH, Haber JE. Cycloheximide-resistant temperature-sensitive lethal mutations of Saccharomyces cerevisiae. Genetics. 1988 Jun;119(2):303–315. [PMC free article] [PubMed]
  • Naumov GI, Korhola M, Naumova ES, Beritashvili DR, Lanto R. Molekuliarnoe kaiotipirovanie biologicheskikh vidov Saccharomyces cerevisiae, S. paradoxus i S. bayanus. Dokl Akad Nauk SSSR. 1990;311(5):1242–1246. [PubMed]
  • Naumov GI, Naumova ES, Lantto RA, Louis EJ, Korhola M. Genetic homology between Saccharomyces cerevisiae and its sibling species S. paradoxus and S. bayanus: electrophoretic karyotypes. Yeast. 1992 Aug;8(8):599–612. [PubMed]
  • New L, Liu K, Crouse GF. The yeast gene MSH3 defines a new class of eukaryotic MutS homologues. Mol Gen Genet. 1993 May;239(1-2):97–108. [PubMed]
  • Prolla TA, Christie DM, Liskay RM. Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene. Mol Cell Biol. 1994 Jan;14(1):407–415. [PMC free article] [PubMed]
  • Prolla TA, Pang Q, Alani E, Kolodner RD, Liskay RM. MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch repair in yeast. Science. 1994 Aug 19;265(5175):1091–1093. [PubMed]
  • Radman M, Wagner R. Mismatch repair in Escherichia coli. Annu Rev Genet. 1986;20:523–538. [PubMed]
  • Radman M, Wagner R. Mismatch recognition in chromosomal interactions and speciation. Chromosoma. 1993 Jun;102(6):369–373. [PubMed]
  • Rayssiguier C, Thaler DS, 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. [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]
  • 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]
  • Rockmill B, Roeder GS. The yeast med1 mutant undergoes both meiotic homolog nondisjunction and precocious separation of sister chromatids. Genetics. 1994 Jan;136(1):65–74. [PMC free article] [PubMed]
  • Ross-Macdonald P, Roeder GS. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell. 1994 Dec 16;79(6):1069–1080. [PubMed]
  • Rothstein RJ. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. [PubMed]
  • Scherer S, Davis RW. Replacement of chromosome segments with altered DNA sequences constructed in vitro. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4951–4955. [PMC free article] [PubMed]
  • Selva EM, New L, Crouse GF, Lahue RS. Mismatch correction acts as a barrier to homeologous recombination in Saccharomyces cerevisiae. Genetics. 1995 Mar;139(3):1175–1188. [PMC free article] [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Takahashi NK, Yamamoto K, Kitamura Y, Luo SQ, Yoshikura H, Kobayashi I. Nonconservative recombination in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5912–5916. [PMC free article] [PubMed]
  • te Riele H, Maandag ER, Berns A. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc Natl Acad Sci U S A. 1992 Jun 1;89(11):5128–5132. [PMC free article] [PubMed]
  • Vallen EA, Hiller MA, Scherson TY, Rose MD. Separate domains of KAR1 mediate distinct functions in mitosis and nuclear fusion. J Cell Biol. 1992 Jun;117(6):1277–1287. [PMC free article] [PubMed]
  • Waldman AS, Liskay RM. Dependence of intrachromosomal recombination in mammalian cells on uninterrupted homology. Mol Cell Biol. 1988 Dec;8(12):5350–5357. [PMC free article] [PubMed]
  • Wang TC, Smith KC. Inviability of dam recA and dam recB cells of Escherichia coli is correlated with their inability to repair DNA double-strand breaks produced by mismatch repair. J Bacteriol. 1986 Mar;165(3):1023–1025. [PMC free article] [PubMed]
  • Wicksteed BL, Collins I, Dershowitz A, Stateva LI, Green RP, Oliver SG, Brown AJ, Newlon CS. A physical comparison of chromosome III in six strains of Saccharomyces cerevisiae. Yeast. 1994 Jan;10(1):39–57. [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]
  • 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. [PMC free article] [PubMed]
  • Wu X, Haber JE. MATa donor preference in yeast mating-type switching: activation of a large chromosomal region for recombination. Genes Dev. 1995 Aug 1;9(15):1922–1932. [PubMed]
  • Xu L, Kleckner N. Sequence non-specific double-strand breaks and interhomolog interactions prior to double-strand break formation at a meiotic recombination hot spot in yeast. EMBO J. 1995 Oct 16;14(20):5115–5128. [PMC free article] [PubMed]
  • Yamamoto K, Kusano K, Takahashi NK, Yoshikura H, Kobayashi I. Gene conversion in the Escherichia coli RecF pathway: a successive half crossing-over model. Mol Gen Genet. 1992 Jul;234(1):1–13. [PubMed]
  • Yokochi T, Kusano K, Kobayashi I. Evidence for conservative (two-progeny) DNA double-strand break repair. Genetics. 1995 Jan;139(1):5–17. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...