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 uracil base from the deoxyribose. As one of the best studied DNA glycosylases, a coherent and complete functional mechanism is emerging that combines structural and biochemical results. This functional mechanism addresses the detection 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 solutions that UDG has evolved to overcome the challenges of policing the genome are shared by other DNA glycosylases and DNA repair enzymes, and thus appear to be general.
Parikh
S S
SS
Department of Molecular Biology, Skaggs Institute for Chemical Biology, The Scripps Research Institute, MB4, 10550 North Torrey Pines Road, La Jolla, CA 92037-1027, USA.
Putnam
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CD
Tainer
J A
JA
D000595:Amino Acid Sequence; D001080:Apurinic Acid / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry / Q000502:physiology; D020137:Base Pair Mismatch; D020029:Base Pairing; D019757:Carbon-Oxygen Lyases / Q000502:physiology; D002384:Catalysis; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D045647:DNA Glycosylases; D011088:DNA Ligases / Q000502:physiology; D004260:DNA Repair / Q000502:physiology; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019143:Evolution, Molecular; D006801:Humans; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000502:physiology; D009690:Nucleic Acid Conformation; D017354:Point Mutation; D011487:Protein Conformation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014498:Uracil / Q000378:metabolism; D051981:Uracil-DNA Glycosidase
D001426:Bacterial Proteins; D046911:Macromolecular Substances; D001080:Apurinic Acid; D014498:Uracil; D004247:DNA; D043223:Deoxyribonuclease IV (Phage T4-Induced); D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D019757:Carbon-Oxygen Lyases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D011088:DNA Ligases