DNA Mismatch Repair: From Structure to Mechanism

Mismatches in a DNA duplex are mainly due to DNAbiosynthetic errors that are generated by DNA polymeraseand escape proofreading mechanisms (Minnick andKunkel 1996). MutS, MutL, and MutH are necessary andsufficient to initiate methyl-dependent mismatch repair inEscherichia coli (for review, see Modrich and Lahue1996). MutS possesses an ATPase activity and initiates repair by recognizing DNA containing mispaired or unpaired nucleotides (Haber and Walker 1991; Modrich1991). After binding to a mismatch, MutS recruits MutL tomediate the activation of an endonuclease, MutH, thatcleaves the newly synthesized strand 5′ to a transiently unmethylated d(GATC) sequence. Both MutS and MutL alsohave essential roles in the subsequent removal and resynthesis of the daughter strand (Modrich and Lahue 1996)...