ATP-DEPENDENT INTERACTION OF HUMAN MISMATCH REPAIR PROTEINS AND DUAL ROLE OF PCNA IN MISMATCH REPAIR

DNA mismatch repair ensures genomic stability by correcting biosynthet ic errors and by blocking homologous recombination. MutS-like and MutL -like proteins play important roles in these processes. In Escherichia coli and yeast these two types of proteins form a repair initiation c omplex that binds to mismatched DNA, However, whether human MutS and M utL homologs interact to form a complex has not been elucidated, Using immunoprecipitation and Western blot analysis we show here that human MSH2, MLH1, PMS2 and proliferating cell nuclear antigen (PCNA) can be co-immunoprecipitated, suggesting formation of a repair initiation co mplex among these proteins. Formation of the initiation complex is dep endent on ATP hydrolysis and at least functional MSH2 and MLH1 protein s, because the complex could not be detected in tumor cells that produ ce truncated MLH1 or MSH2 protein. We also demonstrate that PCNA is re quired in human mismatch repair not only at the step of repair initiat ion, but also at the step of repair DNA re-synthesis.