Uracil DNA glycosylase: Insights from a master catalyst

The recognition and removal of damaged bases in the genome is the province of a highly specialized assemblage of enzymes known as DNA glycosylases. In recent years, structural and mechanistic studies have rapidly moved forwar d such that in some cases, the high-resolution structures of all stable com plexes along the reaction pathway are available. In parallel, advances in i sotopic labeling of DNA have allowed the determination of a transition stat e structure of a DNA repair glycosylase using kinetic isotope effect method s. The use of stable substrate analogs and fluorescent probes have provided methods for real time measurement of the critical step of damaged base fli pping. Taken together, these synergistic structural and chemical approaches have elevated our understanding of DNA repair enzymology to the level prev iously attained in only a select few enzymatic systems. This review summari zes recent studies of the paradigm enzyme, uracil DNA glycosylase, and disc usses future areas for investigation in this field. (C) 2001 Elsevier Scien ce.