Document Type




Format of Original

14 p.

Publication Date



American Chemical Society

Source Publication


Source ISSN



Prokaryotic MutS and eukaryotic Msh proteins recognize base pair mismatches and insertions or deletions in DNA and initiate mismatch repair. These proteins function as dimers (and perhaps higher order oligomers) and possess an ATPase activity that is essential for DNA repair. Previous studies of Escherichia coli MutS and eukaryotic Msh2−Msh6 proteins have revealed asymmetry within the dimer with respect to both DNA binding and ATPase activities. We have found the Thermus aquaticus MutS protein amenable to detailed investigation of the nature and role of this asymmetry. Here, we show that (a) in a MutS dimer one subunit (S1) binds nucleotide with high affinity and the other (S2) with 10-fold weaker affinity, (b) S1 hydrolyzes ATP rapidly while S2 hydrolyzes ATP at a 30−50-fold slower rate, (c) mismatched DNA binding to MutS inhibits ATP hydrolysis at S1 but slow hydrolysis continues at S2, and (d) interaction between mismatched DNA and MutS is weakened when both subunits are occupied by ATP but remains stable when S1 is occupied by ATP and S2 by ADP. These results reveal key MutS species in the ATPase pathway; S1ADP−S2ATP is formed preferentially in the absence of DNA or in the presence of fully matched DNA, while S1ATP−S2ATP and S1ATP−S2ADP are formed preferentially in the presence of mismatched DNA. These MutS species exhibit differences in interaction with mismatched DNA that are likely important for the mechanism of MutS action in DNA repair.


Accepted version. Biochemistry, Vol. 43, No. 41 (October 2004): 13115–13128. DOI. © 2004 American Chemical Society Publications. Used with permission.

Edwin Antony was affiliated with Wesleyan University at time of publication.

antony_7538acc.docx (257 kB)
ADA Accessible Version

Included in

Biology Commons