Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent mismatch repair.
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.
Marsischky
G T
GT
Charles A. Dana Division of Human Cancer Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 USA.
Filosi
N
N
Kane
M F
MF
Kolodner
R
R
D000251:Adenosine Triphosphatases; D000483:Alleles; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair / Q000235:genetics*; D004271:DNA, Fungal / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016208:Databases, Factual; D004591:Electrophoresis, Polyacrylamide Gel; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; D000074081:MutS Homolog 3 Protein; D010641:Phenotype; D010802:Phylogeny; D017354:Point Mutation / Q000235:genetics; D011233:Precipitin Tests; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D017931:DNA Primers; D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C081696:MSH3 protein, S cerevisiae; C098790:MSH6 protein, S cerevisiae; D000074081:MutS Homolog 3 Protein; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C489751:MSH2 protein, S cerevisiae; D051719:MutS DNA Mismatch-Binding Protein; D051718:MutS Homolog 2 Protein; C497175:MutS protein, E coli