Saccharomyces cerevisiae pms2 mutations are alleles of MLH1, and pms2-2 corresponds to a hereditary nonpolyposis colorectal carcinoma-causing missense mutation.
A number of mutant Saccharomyces cerevisiae strains having phenotypes consistent with defects in DNA mismatch repair have been described, but not all have been extensively characterized. In this study we demonstrate that the pms2-1 and pms2-2 alleles arise from missense mutations in the MLH1 gene which inactivate MLH1. One of these alleles, pms2-2, causes the same amino acid substitution in a highly conserved region of the known MutL homologs as that caused by a proposed missense mutation observed in a Swedish hereditary nonpolyposis colorectal carcinoma kindred. This observation supports the functional significance of missense mutations found in hereditary nonpolyposis colorectal carcinoma kindreds and indicates that in some cases S. cerevisiae can serve as a useful model system for the analysis of such mutations.
Jeyaprakash
A
A
Department of Entomology and Nematology, University of Florida, Gainesville 32611-0620, USA.
Das Gupta
R
R
Kolodner
R
R
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017124:Conserved Sequence; D017931:DNA Primers / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics*; D005800:Genes, Fungal; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D000070957:MutL Protein Homolog 1; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; D004271:DNA, Fungal; D004273:DNA, Neoplasm; D005656:Fungal Proteins; C088859:MLH1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D000070957:MutL Protein Homolog 1