Recent progress in the biology, chemistry and structural biology of DNA glycosylases.
Since the discovery in 1974 of uracil DNA glycosylase (UDG), the first member of the family of enzymes involved in base excision repair (BER), considerable progress has been made in the understanding of DNA glycosylases, the polypeptides that remove damaged or mispaired DNA bases from DNA. We also know the enzymes that act downstream of the glycosylases, in the processing of abasic sites, in gap filling and in DNA ligation. This article covers the most recent developments in our understanding of BER, with particular emphasis on the mechanistic aspects of this process, which have been made possible by the elucidation of the crystal structures of several glycosylases in complex with their respective substrates, substrate analogues and products. The biological importance of individual BER pathways is also being appreciated through the inactivation of key BER genes in knockout mouse models.
Institute of Medical Radiobiology of the University of Zürich, Zürich, Switzerland. scharer@imr.unizh.ch
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Schärer
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Jiricny
D000595:Amino Acid Sequence; D000818:Animals; D020137:Base Pair Mismatch; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary
D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases