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 requirement is unknown. Saccharomyces cerevisiae RAD14 was identified in a two-hybrid screen using MSH2 as "bait," and pairwise interactions between MSH2 and RAD1, RAD2, RAD3, RAD10, RAD14, and RAD25 subsequently were demonstrated by two-hybrid analysis. MSH2 coimmunoprecipitated specifically with epitope-tagged versions of RAD2, RAD10, RAD14, and RAD25. 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, and msh2 mutations were epistatic to the mutator phenotype observed in NER-deficient strains. These data suggest that MSH2 and possibly other components of DNA mismatch repair exist in a complex with NER proteins, providing a biochemical and genetical basis for these proteins to function in common processes.
Bertrand
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P
Charles A. Dana Division of Human Cancer Genetics, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Tishkoff
D X
DX
Filosi
N
N
Dasgupta
R
R
Kolodner
R D
RD
D020137:Base Pair Mismatch; D001483:Base Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D016133:Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D011503:Transglutaminases; D014466:Ultraviolet Rays
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C082463:RAD4 protein, S pombe; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D004247:DNA; D011503:Transglutaminases; C489751:MSH2 protein, S cerevisiae; D051718:MutS Homolog 2 Protein; C489752:msh2 protein, S pombe