title: A new mechanism for repairing oxidative damage to DNA: (A)BC excinuclease removes AP sites and thymine glycols from DNA.
abstract: Escherichia coli (A)BC excinuclease is the major enzyme responsible for removing bulky adducts, such as pyrimidine dimers and 6-4 photoproducts, from DNA. Mutants deficient in this enzyme are extremely sensitive to UV and UV-mimetic agents, but not to oxidizing agents, or ionizing radiation which damages DNA in part by generating active oxygen species. DNA glycosylases and AP1 endonucleases play major roles in repairing oxidative DNA damage, and thus it has been assumed that nucleotide excision repair has no role in cellular defense against damage by ionizing radiation and oxidative damage. In this study we show that the E. coli nucleotide excision repair enzyme (A)BC excinuclease removes from DNA the two major products of oxidative damage, thymine glycol and the baseless sugar (AP site). We conclude that nucleotide excision repair is an important cellular defense mechanism against oxidizing agents.
authors.affiliation: Department of Biochemistry, School of Medicine, University of North Carolina, Chapel Hill 27599.
authors.forename: J J
authors.initials: JJ
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Sancar
mesh_terms: D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000032:analysis*; D004706:Endodeoxyribonucleases; D004926:Escherichia coli / Q000201:enzymology; D029968:Escherichia coli Proteins; D007700:Kinetics; D010084:Oxidation-Reduction; D010957:Plasmids; D013941:Thymine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; C029389:thymine glycol; D004706:Endodeoxyribonucleases; C036385:endodeoxyribonuclease uvrABC; D013941:Thymine