proteinsinitsabilitytopromote.PDF

Downloaded from on May 15, 2017 - Published by Cold Spring Harbor Laboratory Press Mlhl is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis N e i l Hunter I and Rhona H. Borts 2 Yeast Genetics, Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK In eukaryotes, homologs of the bacterial MutS and MutL proteins function in DNA mismatch repair and recombination pathways. The mutL homolog MLItl is required for nuclear mismatch repair. Previously, cytological analysis of MLHl.deficient mice has implied a role for Mlhl 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 mlhl rash4 double mutant suggests that both genes act in the same pathway to promote crossing-over. All genetic markers analyzed in mlhl 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 mlhl segregation data with that of pmsl, rash2, rash3, and rash6 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 fun