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PMID: 12618391 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

MLH1 mutations differentially affect meiotic functions in Saccharomyces cerevisiae.

Genetics ·Vol. 163 ·No. 2 ·2003-02-00 ·Pages 515-26

Hoffmann ER, Shcherbakova PV, Kunkel TA, Borts RH

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.

MeSH Terms
Adaptor Proteins, Signal Transducing Amino Acid Sequence Aneuploidy Crossing Over, Genetic/physiology DNA Repair/genetics,physiology Fungal Proteins/genetics,metabolism Meiosis/genetics,physiology Molecular Sequence Data MutL Protein Homolog 1 Nondisjunction, Genetic Saccharomyces cerevisiae/genetics,metabolism Saccharomyces cerevisiae Proteins Sequence Alignment
Chemicals
Adaptor Proteins, Signal Transducing Fungal Proteins MLH1 protein, S cerevisiae Saccharomyces cerevisiae Proteins MutL Protein Homolog 1
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hoffmann Eva R
Department of Biochemistry, University of Oxford, Oxford OX1 3Q, United Kingdom.
Shcherbakova Polina V
Kunkel Thomas A
Borts Rhona H
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
0016-6731
DOI
10.1093/genetics/163.2.515
Published
2003-02-00
Pages
515-26
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC1462462
Subset
IM
External Links
PubMed source DOI: 10.1093/genetics/163.2.515 PMC Full Text View journal details
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