A Multi-Function Enzyme for the Repair of DNA Deamination
Dr. Weiguo Cao, Professor
Dept. of Genetics & Biochemistry, Clemson University
Living organisms are exposed to highly reactive nitrogen species (RNS) from endogenous inflammation and in the environment as collectively defined as nitrogen oxides (NOx). Nitrosative stress imposed by exposure to RNS is a subclass of oxidative stress that leads to oxidative deamination in DNA. Through deamination, cytosine (C), adenine (A), and guanine (G) are converted to uracil (U), hypoxanthine (I), and xanthine (X) or oxanine (O), respectively. Endonuclease V (endo V) mediates an evolutionarily well-conserved pathway to repair adenosine deamination in both prokaryotic and eukaryotic organisms including mammals. Endo V is an enzyme that initiates repair of deaminated DNA bases by making an endonucleolytic incision at the 3’ side one nucleotide from a base lesion. The unusual biochemical mechanism of endo V-mediated lesion recognition, multiple endonuclease and exonuclease activities, and their implications in repair pathway will be presented in light of biochemical, structural biological and enzymological investigations. Endo V-mediated DNA repair is an important mechanism in maintaining genome integrity and preventing cancer in mammalian systems.
Host: Dr. Charlie Wei