Abstract
DNA mismatch repair (MMR) is an important genome caretaker system, and is highly conserved from bacteria to humans. MMR corrects base-base mismatches and small insertion / deletion mispairs generated during DNA replication, recombination and repair. In addition, MMR can also repair oxidized base lesions.
MMR consists of four steps: (1) recognization of mismatches in DNA and binding to mismatch
sites (2) creation of a strand break as a starting point for the excision of the mismatched base (3) excision of the nicked strand from the nicked site up to and slightly past the mismatch (4) repair resynthesis and ligation.
In Escherichia coli, MutS, MutL and MutH have been identified as MMR proteins. In human, MSH2, MSH3, MSH6, MLH1, MLH3, PMS1 and PMS2 have been identified. It is well-known
that defects of these genes lead to an increased mutation rate. Several MMR genes, MSH2, MSH6, MLH1 and PMS2 have been identified in C. elegans. C. elegans is an animal model suitable for
studies of aging and lifespan. Our purpose is to evaluate contribution of MMR for lifespan in C. elegans. We measured lifespan and resistance for oxidative damages of each mutants. In addition, we examined various activities of MMR proteins by using purified MMR proteins. In our session, we will report effect of repair of oxidized lesions by MMR proteins on aging and lifespan in C. elegans.
