Lessons learned from structural results on uracil-DNA glycosylase

• Published in: Mutation research Vol. 460; no. 3-4; pp. 183 - 199
• Main Authors: Parikh, Sudip S, Putnam, Christopher D, Tainer, John A
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.08.2000
• Subjects: Amino Acid Sequence; Apurinic Acid - metabolism; Bacterial Proteins - chemistry; Bacterial Proteins - physiology; base excision repair; Base Pair Mismatch; Base Pairing; Carbon-Oxygen Lyases - physiology; Catalysis; Deoxyribonuclease IV (Phage T4-Induced); DNA - metabolism; DNA base excision repair; DNA Damage; DNA Glycosylases; DNA Ligases - physiology; DNA Repair - physiology; DNA-(Apurinic or Apyrimidinic Site) Lyase; Enzyme mechanism; Evolution, Molecular; Humans; Macromolecular Substances; Models, Molecular; Molecular Sequence Data; N-Glycosyl Hydrolases - chemistry; N-Glycosyl Hydrolases - physiology; Nucleic Acid Conformation; Point Mutation; Protein Conformation; Protein structure; Sequence Alignment; Sequence Homology, Amino Acid; Structure-Activity Relationship; Uracil - metabolism; Uracil-DNA Glycosidase; Uracil-DNA glycosylase; Uracil-DNA glycosylase; Enzyme mechanism; DNA base excision repair; Protein structure
• ISSN: 0921-8777; 0027-5107; 1386-1476
• DOI: 10.1016/S0921-8777(00)00026-4

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.