PURIFIED HUMAN MSH2 PROTEIN BINDS TO DNA CONTAINING MISMATCHED NUCLEOTIDES

The human hMSH2 protein is a member of a highly conserved family of po streplication mismatch repair components found from bacteria to humans . Alterations of the gene coding for this protein cosegregate with, an d are the likely cause of, chromosome 2-linked hereditary nonpolyposis colon cancer. Postreplication mismatch repair has been found to faith fully replace misincorporated nucleotides, thereby increasing the over all fidelity of DNA replication. Loss of postreplication mismatch repa ir function leads to a mutator phenotype, which is proposed to account for the multiple mutations required for multistep carcinogenesis. Alt hough the functions of hMSH2 can be anticipated based on its similarit y to well-characterized bacterial and yeast proteins, proof of its fun ctions has not been established. Here we demonstrate that purified hMS H2 binds specifically to mismatched nucleotides, providing a target fo r the excision repair processes characteristic of postreplication mism atch repair.