• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Mar 1995; 139(3): 1175–1188.
PMCID: PMC1206448

Mismatch Correction Acts as a Barrier to Homeologous Recombination in Saccharomyces Cerevisiae

Abstract

A homeologous mitotic recombination assay was used to test the role of Saccharomyces cerevisiae mismatch repair genes PMS1, MSH2 and MSH3 on recombination fidelity. A homeologous gene pair consisting of S. cerevisiae SPT15 and its S. pombe homolog were present as a direct repeat on chromosome V, with the exogenous S. pombe sequences inserted either upstream or downstream of the endogenous S. cerevisiae gene. Each gene carried a different inactivating mutation, rendering the starting strain Spt15(-). Recombinants that regenerated SPT15 function were scored after nonselective growth of the cells. In strains wild type for mismatch repair, homeologous recombination was depressed 150- to 180-fold relative to homologous controls, indicating that recombination between diverged sequences is inhibited. In one orientation of the homeologous gene pair, msh2 or msh3 mutations resulted in 17- and 9.6-fold elevations in recombination and the msh2 msh3 double mutant exhibited an 43-fold increase, implying that each MSH gene can function independently in trans to prevent homeologous recombination. Homologous recombination was not significantly affected by the msh mutations. In the other orientation, only msh2 strains were elevated (12-fold) for homeologous recombination. A mutation in MSH3 did not affect the rate of recombination in this orientation. Surprisingly, a pms1 deletion mutant did not exhibit elevated homeologous recombination.

Full Text

The Full Text of this article is available as a PDF (1.3M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • 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]
  • Borts RH, Haber JE. Meiotic recombination in yeast: alteration by multiple heterozygosities. Science. 1987 Sep 18;237(4821):1459–1465. [PubMed]
  • Eisenmann DM, Dollard C, Winston F. SPT15, the gene encoding the yeast TATA binding factor TFIID, is required for normal transcription initiation in vivo. Cell. 1989 Sep 22;58(6):1183–1191. [PubMed]
  • Fikes JD, Becker DM, Winston F, Guarente L. Striking conservation of TFIID in Schizosaccharomyces pombe and Saccharomyces cerevisiae. Nature. 1990 Jul 19;346(6281):291–294. [PubMed]
  • Fishman-Lobell J, Rudin N, Haber JE. Two alternative pathways of double-strand break repair that are kinetically separable and independently modulated. Mol Cell Biol. 1992 Mar;12(3):1292–1303. [PMC free article] [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]
  • Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. [PubMed]
  • Harris S, Rudnicki KS, Haber JE. Gene conversions and crossing over during homologous and homeologous ectopic recombination in Saccharomyces cerevisiae. Genetics. 1993 Sep;135(1):5–16. [PMC free article] [PubMed]
  • Kang YS, Kane J, Kurjan J, Stadel JM, Tipper DJ. Effects of expression of mammalian G alpha and hybrid mammalian-yeast G alpha proteins on the yeast pheromone response signal transduction pathway. Mol Cell Biol. 1990 Jun;10(6):2582–2590. [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]
  • Lin FL, Sperle K, Sternberg N. Model for homologous recombination during transfer of DNA into mouse L cells: role for DNA ends in the recombination process. Mol Cell Biol. 1984 Jun;4(6):1020–1034. [PMC free article] [PubMed]
  • Malone RE, Kim S, Bullard SA, Lundquist S, Hutchings-Crow L, Cramton S, Lutfiyya L, Lee J. Analysis of a recombination hotspot for gene conversion occurring at the HIS2 gene of Saccharomyces cerevisiae. Genetics. 1994 May;137(1):5–18. [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]
  • Miret JJ, Milla MG, Lahue RS. Characterization of a DNA mismatch-binding activity in yeast extracts. J Biol Chem. 1993 Feb 15;268(5):3507–3513. [PubMed]
  • Modrich P. Mechanisms and biological effects of mismatch repair. Annu Rev Genet. 1991;25:229–253. [PubMed]
  • Morrison A, Johnson AL, Johnston LH, Sugino A. Pathway correcting DNA replication errors in Saccharomyces cerevisiae. EMBO J. 1993 Apr;12(4):1467–1473. [PMC free article] [PubMed]
  • Poon D, Schroeder S, Wang CK, Yamamoto T, Horikoshi M, Roeder RG, Weil PA. The conserved carboxy-terminal domain of Saccharomyces cerevisiae TFIID is sufficient to support normal cell growth. Mol Cell Biol. 1991 Oct;11(10):4809–4821. [PMC free article] [PubMed]
  • Priebe SD, Westmoreland J, Nilsson-Tillgren T, Resnick MA. Induction of recombination between homologous and diverged DNAs by double-strand gaps and breaks and role of mismatch repair. Mol Cell Biol. 1994 Jul;14(7):4802–4814. [PMC free article] [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]
  • Ray BL, White CI, Haber JE. Heteroduplex formation and mismatch repair of the "stuck" mutation during mating-type switching in Saccharomyces cerevisiae. Mol Cell Biol. 1991 Oct;11(10):5372–5380. [PMC free article] [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]
  • 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]
  • Rothstein RJ. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. [PubMed]
  • Schiestl RH, Gietz RD. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier. Curr Genet. 1989 Dec;16(5-6):339–346. [PubMed]
  • Sikorski RS, 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. [PMC free article] [PubMed]
  • Symington LS, Petes TD. 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. [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]
  • 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]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

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...