PreprintCited by 581DNA Repair MechanismsGenetic factors in colorectal cancerFungal and yeast genetics research

Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair

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Marsischky, G T, Filosi, N, Kane, M F, Kolodner, R·1996·Genes & Development

Abstract

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 in these strains were similar, although slightly lower in magnitude, to those observed previously in the model yeast S. cerevisiae.

    “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).”

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Research works printed but not linked: 2

  1. Bhattacharyya, N.P., A. Skandalis, A. Ganesh, J. Groden, and M. Meuth. 1994. Mutator phenotype in human colorectal car- cinoma cell lines. Proc. Natl. Acad Sci. 91: 6319-6323.
  2. Sherman, F., G.R. Fink, and J.B. Hicks. 1986. Yeast DNA isola- tions. In Methods in yeast genetics, pp. 125--134. Gold Spring Harbor Laboratory, Cold Spring Harbor, NY

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Authors
Marsischky, G. T., Filosi, N., Kane, M. F., & Kolodner, R.
Affiliations
Dana-Farber Cancer Institute (US)
Venue
Genes & Development
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
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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