DNA Mismatch Repair

DNA mismatch repair (MMR) corrects replication errors in newly synthesized DNA. It also has an antirecombination action on heteroduplexes that contain similar but not identical sequences. This review focuses on the genetics and development of MMR and not on the latest biochemical mechanisms. The main focus is on MMR in Escherichia coli, but examples from Streptococcuspneumoniae and Bacillussubtilis have also been included. In most organisms, only MutS (detects mismatches) and MutL (an endonuclease) and a single exonucleaseare present. How this system discriminates between newlysynthesized and parental DNA strands is not clear. In E. coli and its relatives, however, Dam methylation is an integral part of MMR and is the basis for strand discrimination. A dedicated site-specific endonuclease, MutH, is present, andMutL has no endonuclease activity; four exonucleases can participate in MMR. Although it might seem that the accumulated wealth of genetic and biochemical data has given us a detailed picture of the mechanism of MMR in E. coli, the existence of three competing models to explain the initiation phase indicates the complexity of the system. The mechanism of the antirecombination action of MMR is largely unknown, but only MutS and MutL appear to be necessary. A primary site of action appears to be on RecA, although subsequent steps of the recombination process can also be inhibited. In this review, the genetics of Very Short Patch (VSP) repair of T/G mismatches arising from deamination of 5-methylcytosineresidues is also discussed.