Analysis of conditional mutations in the Saccharomyces cerevisiae MLH1 gene in mismatch repair and in meiotic crossing over.

Genetics
Juan Lucas ArguesoEric Alani

Abstract

In mismatch repair (MMR), members of the MLH gene family have been proposed to act as key molecular matchmakers to coordinate mismatch recognition with downstream repair functions that result in mispair excision. Two members of this gene family, MLH1 and MLH3, have also been implicated in meiotic crossing over. These diverse roles suggest that a mutational analysis of MLH genes could provide reagents required to identify interactions between gene products and to test whether the different roles ascribed to a subset of these genes can be separated. In this report we show that in Saccharomyces cerevisiae the mlh1Delta mutation confers inviability in pol3-01 strain backgrounds that are defective in the Poldelta proofreading exonuclease activity. This phenotype was exploited to identify four mlh1 alleles that each confer a temperature-sensitive phenotype for viability in pol3-01 strains. In three different mutator assays, strains bearing conditional mlh1 alleles displayed wild-type or nearly wild-type mutation rates at 26 degrees. At 35 degrees, these strains exhibited mutation rates that approached those observed in mlh1Delta mutants. The mutator phenotype exhibited in mlh1-I296S strains was partially suppressed at 35 degrees by E...Continue Reading

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Citations

Oct 7, 2003·Annual Review of Microbiology·Mark J Schofield, Peggy Hsieh
Feb 24, 2006·Proceedings of the National Academy of Sciences of the United States of America·Julie Akiko HeckEric Alani
Oct 7, 2004·Cytogenetic and Genome Research·E R Hoffmann, R H Borts
Nov 26, 2003·Journal of Evolutionary Biology·D GreigR H Borts
Mar 10, 2004·Microbiology and Molecular Biology Reviews : MMBR·Katherine A BorkovichRobert Pratt
Jun 1, 2002·The Journal of Biological Chemistry·Takuro Nakagawa, Richard D Kolodner
Jul 19, 2002·Yeast

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