The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.
The mechanism of DNA mismatch repair has been modeled upon biochemical studies of the E. coli DNA adenine methylation-instructed pathway where the initial recognition of mismatched nucleotides is performed by the MutS protein. MutS homologs (MSH) have been identified based on a highly conserved region containing a Walker-A adenine nucleotide ... binding motif. Here we show that adenine nucleotide binding and hydrolysis by the human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch. The hMSH2-hMSH6 complex is ON (binds mismatched nucleotides) in the ADP-bound form and OFF in the ATP-bound form. These results suggest a new model for the function of MutS proteins during mismatch repair in which the switch determines the timing of downstream events.
Mesh Terms:
Adenosine Diphosphate, Adenosine Triphosphate, DNA Footprinting, DNA Repair, DNA-Binding Proteins, Eukaryotic Initiation Factor-2, GTP Phosphohydrolases, Guanine Nucleotide Exchange Factors, Humans, Hydrolysis, Macromolecular Substances, MutS Homolog 2 Protein, Proteins, Proto-Oncogene Proteins
Adenosine Diphosphate, Adenosine Triphosphate, DNA Footprinting, DNA Repair, DNA-Binding Proteins, Eukaryotic Initiation Factor-2, GTP Phosphohydrolases, Guanine Nucleotide Exchange Factors, Humans, Hydrolysis, Macromolecular Substances, MutS Homolog 2 Protein, Proteins, Proto-Oncogene Proteins
Cell
Date: Dec. 26, 1997
PubMed ID: 9428522
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