Methyl-directed DNA Mismatch Correction

In 1964 Robin Holliday (1) proposed the correction of DNA base pair mismatches within recombination intermediates as the basis for gene conversion. The existence of the mismatch repair systems implied by this proposal is now well established. Activities that recognize and process base pairing errors within the DNA helix have been identified in bacteria, fungi, and mammalian cells. However, the functions and mechanisms of such systems are best understood in Escherichia coli, an organism that possesses at least three distinct mismatch correction pathways. These three systems are involved not only in the processing of recombination intermediates but also contribute in a major way to the genetic stability of the organism, a function anticipated for mismatch repair by Tiraby and Fox and by Wagner and Meselson. The significance of mismatch correction in the maintenance of low spontaneous mutability becomes apparent when one considers that seven E. coli mutator genes (dam, mutD, mutH, mutL, mutS, mutU, and mutY) have been implicated in mismatch repair. This minireview will summarize information on the most extensively studied E. coli system for mismatch correction, the methyl-directed pathway for processing of DNA biosynthetic errors and intermediates in genetic recombination. A discussion of other E. coli mismatch correction systems may be found in the recent literature and in several recent reviews. Mismatch repair pathways in other organisms and descriptions of the structural properties of mispaired bases may also be found in several of these reviews.