Genetic evidence for the nature, and excision repair, of DNA lesions resulting from incorporation of 5-bromouracil.
Escherichia coli mutants defective in DNA uracil N-glycosidase (ung-) or endonuclease VI active against apurinic/apyrimidinic sites in DNA (xthA-) exhibit enhanced sensitivity towards 5-bromodeoxyuridine relative to the wild type strain, pointing to involvement of these enzymes in repair of bromouracil-induced lesions in DNA. Mutants defective in DNA polymerase I, either in polymerizing activity (polAl-) or (5' leads to 3')-exonuclease activity (polA107-) exhibit unusually high sensitivity (including marked lethality) in the presence of 5-bromodeoxyuridine. The results indicate that DNA polymerase I, and its associated (5'--3')-exonuclease activity, are involved in repair of bromouracil-induced lesions and are not readily replaced, if at all, by DNA polymerases II and III. Thermosensitive mutant in DNA ligase gene (lig ts7) shows high sensitivity towards 5-bromodeoxyuridine at 42 degrees C indicating the role of the enzyme in repair of bromouracil-induced lesions in DNA. Involvement of DNA uracil N-glycosidase, and endonuclease active against apurinic/apyrimidinic sites in recognition and repair of 5-bromouracil-induced damage permits of some inferences regarding the nature of this damage (lesions), in particular dehalogenation of incorporated bromouracil to uracil residues.
D001973:Bromodeoxyuridine / Q000494:pharmacology; D001976:Bromouracil / Q000494:pharmacology*; D011088:DNA Ligases / Q000235:genetics; D004256:DNA Polymerase I / Q000235:genetics; D004260:DNA Repair; D004269:DNA, Bacterial / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics*; D006026:Glycoside Hydrolases / Q000235:genetics; D009154:Mutation; D014498:Uracil
D004269:DNA, Bacterial; D001976:Bromouracil; D014498:Uracil; D004256:DNA Polymerase I; D004720:Endonucleases; D006026:Glycoside Hydrolases; D011088:DNA Ligases; D001973:Bromodeoxyuridine