Chemistry and Biology of the Repair of Oxidatively Induced Bulky DNA Lesions
Abstract
Reactive oxygen species (ROS) can be induced by both endogenous and exogenous sources. While maintaining cellular ROS homeostasis is essential for normal cellular function, excess generation of ROS can cause damage to lipids, proteins and DNA. Despite significant amount of work has been carried out for the replication and repair of single-nucleobase lesions induced by ROS, not much is known about bulky DNA lesions are repaired in human cells. In this presentation, the speaker will describe the use of LC-MS/MS/MS for assessing the formation and repair of two pairs of ROS-induced bulky DNA lesions, i.e., the (5' R) and (S'S) diastereomers of 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) and 8,5'-cyclo-2'-deoxyguanosine (cyclo-dG) in mammalian cells and tissues. The speaker’s research group found that the deficiency in nucleotide excision repair (NER) proteins, XP A and ERCC 1, could give rise to elevated accumulation of endogenously induced cyclo-dA and cyclo-dG in manunalian tissues. He will also discuss the LC-MS/MS coupled with shuttle vector method that his research group developed for examining how these DNA lesions compromise DNA replication and transcription in cells. They found that both cyclo-dA and cyclo-dG substantially blocked DNA replication and transcription in mammalian cells, and they could induce mutations during replication and transcription. Together, the combined chemical and biological approaches provided significant new knowledge about the biological consequences of oxidatively generated bulky DNA lesions.
About the speaker
Prof. Wang Yinsheng received his PhD in Chemistry from Washington University in St. Louis in 2001. He has joined the University of California at Riverside since then, and is currently Professor of Chemistry. He is also Director of the Environmental Toxicology Graduate Program.
Prof. Wang’s research interests are in analytical chemistry and chemical biology. The work of his research group is concentrated on two broadly defined areas, which are DNA damage/mutagenesis and proteomics.
Prof. Wang received prestigious awards including the Biemann Medal and the Chemical Research in Toxicology Young Investigator Award. He is a Fellow of the American Association for the Advancement of Science.
