报告时间：2017年11月21日（周二）下午15:30

报告地点：高等研究院会议室

报告人：刘珈泉

任　职：Research Associate 1, Department of Cancer Biology and Genetics, The Ohio State University

题　目：From diffusion to function——DNA mismatch repair in single molecule

Abstract:

　　Lynch syndrome or hereditary nonpolyposis colorectal cancer (LS/HNPCC), which is now recognized as the most common hereditary cancer predisposition, is caused by defects in the human DNA mismatch repair (MMR) genes. The products of these genes, highly conserved MutS (MSH) and MutL (MLH/PMS) homologs, initiate MMR and act as DNA damage sensors that can trigger apoptosis. The collaborative mechanics of MSH and MLH/PMS proteins have not been resolved in any organism. We have visualized ensemble E.coli (Ec) MMR by single molecule imaging and revealed that MutS sliding clamp is essential to recruit EcMutL onto the mismatched DNA. ATP binding by EcMutL establishes a second long-lived DNA clamp that oscillates between the principal EcMutS-EcMutL complex and unrestricted EcMutS and EcMutL sliding clamps. The EcMutH and EcUvrD that target MMR excision only bind clamped EcMutL, increasing their DNA association kinetics. The assembly of MMR complexes illustrates how cascading stable sliding clamps can modulate 1-dimensional (1D) diffusion mechanics on DNA to direct MMR.