PMID:11454861

Citation	Blackwell, LJ, Bjornson, KP, Allen, DJ and Modrich, P (2001) Distinct MutS DNA-binding modes that are differentially modulated by ATP binding and hydrolysis. J. Biol. Chem. 276:34339-47
Abstract	The role of MutS ATPase in mismatch repair is controversial. To clarify further the function of this activity, we have examined adenine nucleotide effects on interactions of Escherichia coli MutS with homoduplex and heteroduplex DNAs. In contrast to previous results with human MutS alpha, we find that a physical block at one end of a linear heteroduplex is sufficient to support stable MutS complex formation in the presence of ATP.Mg(2+). Surface plasmon resonance analysis at low ionic strength indicates that the lifetime of MutS complexes with heteroduplex DNA depends on the nature of the nucleotide present when MutS binds. Whereas complexes prepared in the absence of nucleotide or in the presence of ADP undergo rapid dissociation upon challenge with ATP x Mg(2+), complexes produced in the presence of ATP x Mg(2+), adenosine 5'-(beta,gamma-imino)triphosphate (AMPPNP) x Mg(2+), or ATP (no Mg(2+)) are resistant to dissociation upon ATP challenge. AMPPNP x Mg(2+) and ATP (no Mg(2+)) reduce MutS affinity for heteroduplex but have little effect on homoduplex affinity, resulting in abolition of specificity for mispaired DNA at physiological salt concentrations. Conversely, the highest mismatch specificity is observed in the absence of nucleotide or in the presence of ADP. ADP has only a limited effect on heteroduplex affinity but reduces MutS affinity for homoduplex DNA.
Links	PubMed Online version:10.1074/jbc.M104256200
Keywords	Adenine/chemistry; Adenosine Triphosphatases/metabolism; Adenosine Triphosphate/metabolism; Adenylyl Imidodiphosphate/pharmacology; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Base Pair Mismatch; Cations/metabolism; DNA/metabolism; DNA Repair; DNA-Binding Proteins/metabolism; Dose-Response Relationship, Drug; Escherichia coli/metabolism; Escherichia coli Proteins; Hydrolysis; Indicators and Reagents/pharmacology; Kinetics; Magnesium/metabolism; MutS DNA Mismatch-Binding Protein; Nucleic Acid Heteroduplexes/metabolism; Potassium Chloride/pharmacology; Protein Binding; Streptavidin/pharmacology; Surface Plasmon Resonance; Time Factors
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