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J. Bacteriol. doi:10.1128/JB.01513-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Physical and Functional Interactions between Escherichia coli MutY Glycosylase and Mismatch Repair Protein MutS

Department of Biochemistry and Molecular Biology, University of Maryland at Baltimore, Maryland

^* To whom correspondence should be addressed. Email: aluchang{at}umaryland.edu.

	Abstract

Escherichia coli MutY and MutS increase replication fidelity by removing adenines that were misincorporated opposite to 7,8-dihydro-8-oxo-deoxyguanines (8-oxoG), G, or C. MutY DNA glycosylase removes adenines from these mismatches through a short-patch base excision repair pathway and thus prevents G:C to T:A and A:T to G:C mutations. MutS binds to the mismatches and initiate the long-patch mismatch repair on daughter DNA strands. We have previously reported that human MutY homolog (hMYH) physically and functionally interacts with the human MutS homolog, hMutS (Gu et al. 2002. J. Biol. Chem. 277:11135-11142). Here, we show that a similar relationship between MutY and MutS exists in E. coli. The interaction of MutY and MutS involves the Fe-S domain of MutY and the ATPase domain of MutS. MutS, in 8-fold molar excess over MutY, can enhance the binding activity of MutY with an A/8-oxoG mismatch by 8-fold. The MutY expression level and activity in mutS mutant strains are 6-fold and 2-fold greater, respectively, as compared to the wild-type cells. The frequency of A:T to G:C mutations is reduced by 2-3 fold in a mutSmutY mutant as compared to a mutS mutant. Our results suggest that MutY base excision repair and mismatch repair defend against the mutagenic effect of 8-oxoG lesions in a cooperative manner.