报告人：Hong Ling 教授 (Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, Canada)
报告题目：Structural insight into cancer related DNA damage response
Translesion DNA synthesis (TLS) is an important DNA-damage-response mechanism. In TLS, specialized DNA polymerases (mostly Y-family polymerases) replicate through DNA damage sites. The transleional DNA polymerases are error-prone in replication and exhibit diverse specificities in bypassing DNA lesions. One of the focuses in TLS research is to reveal the molecular basis of TLS in replication over DNA damage sites and making mutations. The crystal structures of Y-family polymerase/DNA (with cancer related lesions) complexes will be presented in this talk. The structural work demonstrates two different mechanisms in bypassing environmental pollutant-generated DNA lesions. One mechanism is demonstrated by error-prone TLS replication, which accounts for pollution-induced mutagenesis/carcinogenesis, the other is illustrated by error-free replication for protection of cells from harmful carcinogens.
Research in the Ling laboratory focuses on identifying the molecular mechanisms of DNA damage and how this is properly managed in cells. Particularly, we study biological responses to DNA damage and mutagenesis caused by endogenous and environmental DNA-damaging agents, which have broad implications in cancer. To reach our research goals, we use X-ray crystallography to determine protein structures, combined with molecular biology, cell biology, protein chemistry and other biophysical methods. We currently have three main projects: 1) Translesion DNA synthesis and its regulation, 2) Human Y-family polymerases and carcinogenesis/drug resistance, 3) Error-free DNA lesion bypass. Our work has been published in Cell, Nature, EMBOJ, PNAS and other high impact scientific journals. The Ling lab is currently funded by The Canadian Institutes of Health Research (CIHR), The Natural Science and Engineering Research Council of Canada (NSERC) and The Cancer Research Society (CRS).