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MLH1 Mutations Differentially Affect Meiotic Functions in Saccharomyces cerevisiae
journal contribution
posted on 2023-06-08, 05:52 authored by Eva R Hoffmann, Polina V Shcherbakova, Thomas A Kunkel, Rhona H BortsTo 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.
History
Publication status
- Published
Journal
GeneticsISSN
0016-6731Issue
2Volume
163Page range
515-526Pages
12.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
Contribution: experimental design, data collection, data analysis, and writing the paper. Funding was awarded to senior author.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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