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Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair
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Saccharomyces cerevisiae encodes six genes, MSH1-6, which encode proteins related to the bacterial MutS protein. In this study the role of MSH2, MSH3, and MSH6 in mismatch repair has been examined by measuring the rate of accumulating mutations and mutation spectrum in strains containing different combinations of msh2, msh3, and msh6 mutations and by studying the physical interaction between the MSH2 protein and the MSH3 and MSH6 proteins. The results indicate that S. cerevisiae has two pathways of MSH2-dependent mismatch repair: one that recognized single-base mispairs and requires MSH2 and MSH6, and a second that recognizes insertion/deletion mispairs and requires a combination of either MSH2 and MSH6 or MSH2 and MSH3. The redundancy of MSH3 and MSH6 explains the greater prevalence of hmsh2 mutations in HNPCC families and suggests how the role of hmsh3 and hmsh6 mutations in cancer susceptibility could be analyzed.
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“Increases in mutation rate were similar, although slightly lower in magnitude, to those observed previously in the model yeast S. cerevisiae, where msh2 mutations increase resistance rate to Canavanine by 40 fold compared to 6.8 fold for 5-FOA here, or reversion of a 7xT run in a HOM3 mutant by 662 fold compared to 120 fold for 7xC in FRR1 here (Marsischky et al., 1996).”
From Natural mismatch repair mutations mediate phenotypic diversity and drug resistance in Cryptococcus deuterogattii (2017) · cites this paper as Marsischky et al., 1996
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Self-citation
Metadata
- Authors
- Marsischky, G. T., Filosi, N., Kane, M. F., & Kolodner, R.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1996-02-15
- Volume
- 10
- Issue
- 4
- Pages
- 407-420
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2170472485
- Cited by
- 581
- References
- 58
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 14 · 2022: 12 · 2021: 16 · 2020: 7 · 2019: 11 · 2018: 5 · 2017: 14 · 2016: 6 · 2015: 13 · 2014: 18 · 2013: 20 · 2012: 9
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (CA06516)
- National Cancer Institute (CA06516, P30CA006516)
- National Institute of General Medical Sciences (GM50006, R01GM050006)
- National Institute of Allergy and Infectious Diseases (AI28691, P30AI028691)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- DNA mismatch repair, MSH2, MSH3, MSH6, MSH1, Saccharomyces cerevisiae, protein-protein interaction, mutation spectrum, mutation rate, Lynch syndrome, cancer susceptibility, MutS homologs
- MeSH terms
- MutS Homolog 3 Protein, Adenosine Triphosphatases, Alleles, Amino Acid Sequence, Bacterial Proteins, Base Sequence, DNA Repair, DNA-Binding Proteins, DNA, Fungal, Electrophoresis, Polyacrylamide Gel, Fungal Proteins, Genes, Fungal, Models, Genetic, Molecular Sequence Data, Phenotype, Phylogeny, Precipitin Tests, Saccharomyces cerevisiae, Databases, Factual, Sequence Alignment, Point Mutation, Sequence Homology, Amino Acid, Sequence Analysis, DNA Primers, Saccharomyces cerevisiae Proteins, Escherichia coli Proteins, MutS Homolog 2 Protein, MutS DNA Mismatch-Binding Protein
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