Recent progress in the biology, chemistry and structural biology of DNA glycosylases

Since the discovery in 1974 of uracil DNA glycosylase (UDG), the first memb er of the family of enzymes involved in base excision repair (BER), conside rable progress has been made in the understanding of DNA glycosylases, the polypeptides that remove damaged or mispaired DNA bases from DNA. We also k now the enzymes that act downstream of the glycosylases, in the processing of abasic sites, in gap filling and in DNA ligation. This article covers th e most recent developments in our understanding of BER, with particular emp hasis on the mechanistic aspects of this process, which have been made poss ible by the elucidation of the crystal structures of several glycosylases i n complex with their respective substrates, substrate analogues and product s. The biological importance of individual BER pathways is also being appre ciated through the inactivation of key BER genes in knockout mouse models. BioEssays 23:270-281, 2001. (C) 2001 John Wiley & Sons, Inc.