Lessons learned from structural results on uracil-DNA glycosylase

Uracil-DNA glycosylase (UDG) functions as a sentry guarding against uracil in DNA. UDG initiates DNA base excision repair (BER) by hydrolyzing the ura cil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines str uctural and biochemical results. This functional mechanism addresses the de tection of uracil bases within a vast excess of normal DNA, the features of the enzyme that drive catalysis, and coordination of UDG with later steps of BER while preventing the release of toxic intermediates. Many of the sol utions that UDG has evolved to overcome the challenges of policing the geno me are shared by other DNA glycosylases and DNA repair enzymes, and thus ap pear to be general. (C) 2000 Elsevier Science B.V. All rights reserved.