Date: 2009. 7. 15, 5:00 PM Place: Mogam Hall, Bldg 500 -Abstract- Genomic DNA is constantly attacked by endogenous and exogenous DNA damaging agents, such as UV radiation, alkylating agents, and reactive oxygen species. These agents generate a wide variety of genotoxic lesions, which if left unrepaired could lead to mutagenesis and eventually the development of various cancers. To counter the deleterious effects of DNA lesions, all known organisms utilize DNA repair systems including direct reversal of alkylation damages, DNA double strand break repair, nucleotide-excision DNA repair, and base-excision DNA repair. The base-excision DNA repair (BER), the major DNA repair pathway, coordinates a series of chemical transformations catalyzed by DNA glycosylase, lyase, endonuclease, polymerase, and ligase, thereby enabling restoration of the original sequence of DNA. Important questions in the BER concern how DNA glycosylases, key components of the BER pathway, specifically recognize their substrate DNA among the millions-fold excess of normal DNA, and catalyze the scission of glycosidic bond of their substrate nucleosides. In this presentation, new insights into these questions that were obtained via chemical modification of substrate DNA will be discussed.