MLH1 Mutations Differentially Affect Meiotic Functions in Saccharomyces cerevisiae

Hoffmann, Eva R, Shcherbakova, Polina V, Kunkel, Thomas A and Borts, Rhona H (2003) MLH1 Mutations Differentially Affect Meiotic Functions in Saccharomyces cerevisiae. Genetics, 163 (2). pp. 515-526. ISSN 0016-6731

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Abstract

To test whether missense mutations in the cancer susceptibility gene MLH1 adversely affect meiosis, we examined 14 yeast MLH1 mutations for effects on meiotic DNA transactions and gamete viability in the yeast Saccharomyces cerevisiae. Mutations analogous to those associated with hereditary nonpolyposis colorectal cancer (HNPCC) or those that reduce Mlh1p interactions with ATP or DNA all impair replicative mismatch repair as measured by increased mutation rates. However, their effects on meiotic heteroduplex repair, crossing over, chromosome segregation, and gametogenesis vary from complete loss of meiotic functions to no meiotic defect, and mutants defective in one meiotic process are not necessarily defective in others. DNA binding and ATP binding but not ATP hydrolysis are required for meiotic crossing over. The results reveal clear separation of different Mlh1p functions in mitosis and meiosis, and they suggest that some, but not all, MLH1 mutations may be a source of human infertility.

Item Type: Article
Additional Information: Contribution: experimental design, data collection, data analysis, and writing the paper. Funding was awarded to senior author.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Eva Hoffmann
Date Deposited: 06 Feb 2012 20:18
Last Modified: 02 Apr 2012 08:53
URI: http://sro.sussex.ac.uk/id/eprint/25336
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