title: Investigations of pyrimidine dimer glycosylases--a paradigm for DNA base excision repair enzymology.
abstract: The most prevalent forms of cancer in humans are the non-melanoma skin cancers, with over a million new cases diagnosed in the United States annually. The portions of the body where these cancers arise are almost exclusively on the most heavily sun-exposed tissues. It is now well established that exposure to ultraviolet light (UV) causes not only damage to DNA that subsequently generates mutations and a transformed phenotype, but also UV-induced immunosuppression. Human cells have only one mechanism to remove the UV-induced dipyrimidine DNA photoproducts: nucleotide excision repair (NER). However, simpler organisms such as bacteria, bacteriophages and some eukaryotic viruses contain up to three distinct mechanisms to initiate the repair of UV-induced dipyrimidine adducts: NER, base excision repair (BER) and photoreversal. This review will focus on the biology and the mechanisms of DNA glycosylase/AP lyases that initiate BER of cis-syn cyclobutane pyrimidine dimers. One of these enzymes, the T4 pyrimidine dimer glycosylase (T4-pdg), formerly known as T4 endonuclease V has served as a model in the study of this entire class of enzymes. It was the first DNA repair enzyme: (1) for which a biologically significant processive nicking activity was demonstrated; (2) to have its active site determined, (3) to have its crystal structure solved, (4) to be shown to carry out nucleotide flipping, and (5) to be used in human clinical trials for disease prevention.
authors.affiliation: Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA. lloydst@ohsu.edu
authors.forename: R Stephen
authors.initials: RS
authors.lastname: Lloyd
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D019281:Dimerization; D008958:Models, Molecular
chemical_list: D045647:DNA Glycosylases; C036401:deoxyribopyrimidine endonucleosidase