Mismatch repair during homologous and homeologous recombination.
Homologous recombination (HR) and mismatch repair (MMR) are inextricably linked. HR pairs homologous chromosomes before meiosis I and is ultimately responsible for generating genetic diversity during sexual reproduction. HR is initiated in meiosis by numerous programmed DNA double-strand breaks (DSBs; several hundred in mammals). A characteristic feature of HR is the exchange of DNA strands, which results in the formation of heteroduplex DNA. Mismatched nucleotides arise in heteroduplex DNA because the participating parental chromosomes contain nonidentical sequences. These mismatched nucleotides may be processed by MMR, resulting in nonreciprocal exchange of genetic information (gene conversion). MMR and HR also play prominent roles in mitotic cells during genome duplication; MMR rectifies polymerase misincorporation errors, whereas HR contributes to replication fork maintenance, as well as the repair of spontaneous DSBs and genotoxic lesions that affect both DNA strands. MMR suppresses HR when the heteroduplex DNA contains excessive mismatched nucleotides, termed homeologous recombination. The regulation of homeologous recombination by MMR ensures the accuracy of DSB repair and significantly contributes to species barriers during sexual reproduction. This review discusses the history, genetics, biochemistry, biophysics, and the current state of studies on the role of MMR in homologous and homeologous recombination from bacteria to humans.
Department of Biochemistry, University of Iowa, Iowa City, Iowa 52242.
Maria
M
Spies
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University Medical Center and Comprehensive Cancer Center, Columbus, Ohio 43210 Human Genetics Institute, The Ohio State University Medical Center, Columbus, Ohio 43210 Physics Department, The Ohio State University, Columbus, Ohio 43210.
Richard
R
Fishel
D000818:Animals; D005075:Biological Evolution; D053903:DNA Breaks, Double-Stranded; D053843:DNA Mismatch Repair / Q000502:physiology*; D059765:Homologous Recombination / Q000502:physiology*; D006801:Humans; D008540:Meiosis / Q000502:physiology*; D008954:Models, Biological; D013045:Species Specificity