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NBC Seminar Single-molecule Studies on DNA Mismatch Repair Speaker: Jong-Bong Lee , Ph.D Department of Physics, POSTECH Real time observation of individual biomolecules and their complex going through reactions enables us to observe transient intermediate states, multiple pathways, and the fluctuation of the molecular properties. The removal of ensemble averaging is capable of elucidating the salient features of the molecular mechanism in a variety of biological processes. It has been studied that DNA repair proteins search a target via a 1dimensional diffusion along naked DNA. Due to the absence of the target on DNA this single-molecule tracking approach lacked of understanding the catalytic function of the repair proteins and moreover the mechanism of the downstream transactions for the repair of an error on the DNA. I will present the catalytic processes of MutS, mismatch repair initiation protein, on a mismatched DNA that bears an unpaired nucleotide. Our single-molecule analysis reveals that MutS undergoes two distinct conformational changes during DNA mismatch repair. MutS forms a transient clamp that scans duplex DNA to find the unpaired nucleotide and a different sliding clamp at the mismatch that is induced by ATP binding. Our studies propose a solution for a highly controversial issue in DNA mismatch repair. I will also tell a story how we use a novel single-molecule technique to study other DNA mismatch proteins such as UvrD helicase and Exonuclease that are involved in the removal of the single-stranded DNA after the strand incision via the downstream signaling of MutS. When: 4:15 PM on Oct. 13 (Thu.) Where: Engineering Building 1, E104 Contact: Prof. HyungJoon Cho (2520) / [email protected] School of Nano-Bioscience & Chemical Engineering UNIST