Dissociation of Mismatch Recognition and ATPase Activity by hMSH2-hMSH3

• Published in: The Journal of biological chemistry Vol. 274; no. 31; pp. 21659 - 21664
• Main Authors: Wilson, Teresa, Guerrette, Shawn, Fishel, Richard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30-07-1999; American Society for Biochemistry and Molecular Biology
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Base Pair Mismatch; Binding Sites; Dimerization; DNA Transposable Elements; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - metabolism; Humans; Kinetics; Multidrug Resistance-Associated Proteins; MutS Homolog 2 Protein; MutS Homolog 3 Protein; Protein Conformation; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - metabolism; Recombinant Fusion Proteins - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Sequence Deletion
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.31.21659

MSH2-MSH3 directs the repair of insertion/deletion loops of up to 13 nucleotides in vivoand in vitro. To examine the biochemical basis of this repair specificity, we characterized the mispair binding and ATPase activity of hMSH2-hMSH3. The ATPase was found to be regulated by a mismatch-stimulated ADP → ATP exchange, which induces a conformational transition by the protein complex. We demonstrated strong binding of hMSH2-hMSH3 to an insertion/deletion loop containing 24 nucleotides that is incapable of provoking ADP → ATP exchange, suggesting that mismatch recognition appears to be necessary but not sufficient to induce the intrinsic ATPase. These studies support the idea that hMSH2-hMSH3 functions as an adenosine nucleotide-regulated molecular switch that must be activated by mismatched nucleotides for classical mismatch repair to occur.