Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis

Neil Hunter, Rhona H. Borts

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

In eukaryotes, homologs of the bacterial MutS and MutL proteins function in DNA mismatch repair and recombination pathways. The mutL homolog MLH1 is required for nuclear mismatch repair. Previously, cytological analysis of MLH1-deficient mice has implied a role for Mlh1 in crossing-over during meiosis. Here we demonstrate that Saccharomyces cerevisiae diploids containing a deletion of MLH1 have reduced crossing-over in addition to a deficiency in the repair of mismatched DNA during meiosis. Absence of either of the meiosis-specific mutS homologs Msh4 or Msh5 results in a similar reduction in crossing-over. Analysis of an mlh1 msh4 double mutant suggests that both genes act in the same pathway to promote crossing-over. All genetic markers analyzed in mlh1 mutants display elevated frequencies of non- Mendelian segregation. Most of these events are postmeiotic segregations that represent unrepaired heteroduplex. These data suggest that either restorational repair is frequent or heteroduplex tracts are shorter in wild- type cells. Comparison of mlh1 segregation data with that of pms1, msh2, msh3, and msh6 mutants show that the ability to promote crossing-over is unique to MLH1. Taken together these observations indicate that both crossing-over and gene conversion require MutS and MutL functions and that Mlh1 represents an overlap between these two pathways. Models of Mlh1 function are discussed.

Original languageEnglish (US)
Pages (from-to)1573-1582
Number of pages10
JournalGenes and Development
Volume11
Issue number12
StatePublished - Jun 15 1997
Externally publishedYes

Fingerprint

DNA Mismatch Repair
Meiosis
Proteins
Gene Conversion
Bacterial Proteins
Eukaryota
Diploidy
Genetic Markers
DNA Repair
Genetic Recombination
Saccharomyces cerevisiae
Genes

Keywords

  • Crossing-over
  • Gene conversion
  • Meiosis
  • Mismatch repair
  • MutL homologs
  • MutS homologs

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. / Hunter, Neil; Borts, Rhona H.

In: Genes and Development, Vol. 11, No. 12, 15.06.1997, p. 1573-1582.

Research output: Contribution to journalArticle

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