PHYSICAL INTERACTION BETWEEN COMPONENTS OF DNA MISMATCH REPAIR AND NUCLEOTIDE EXCISION-REPAIR

Nucleotide excision repair (NER) and DNA mismatch repair are required for some common processes although the biochemical basis for this requ irement is unknown. Saccharomyces cerevisiae RAD14 was identified in a two-hybrid screen using MSH2 as ''bait,'' and pairwise interactions b etween MSH2, and RAD1, RAD2, RAD3, RAD10, RAD14, and RAD25 subsequentl y were demonstrated by two-hybrid analysis. MSH2 coimmunoprecipitated specifically with epitope-tagged versions of RAD2, RAD10, RAD14, and R AD25. MSH2 and RAD10 were found to interact in msh3 msh6 and mlh1 pms1 double mutants, suggesting a direct interaction with MSH2. Mutations in MSH2 increased the UV sensitivity of NER-deficient yeast strains, a nd msh2 mutations were epistatic to the mutator phenotype ob served in NER deficient strains. These data suggest that MSH2 and possibly othe r components of DNA mismatch repair exist in a complex with NER protei ns, providing a biochemical and genetical basis for these proteins to function in common processes.