title: Suppressible base substitution mutations induced by angelicin (isopsoralen) in the Escherichia coli lacI gene: implications for the mechanism of SOS mutagenesis.
abstract: Angelicin- plus near-UV-induced mutations were umuC dependent in Escherichia coli K-12. Angelicin, a monofunctional psoralen derivative, is believed to damage DNA almost exclusively at pyrimidine bases. To broaden our knowledge about the mutagenic specificity of SOS-dependent mutagens, we determined the mutational specificity of 233 suppressible lacI mutations induced by angelicin. More than 90% of the nonsense mutations arose via transversion substitutions. The three most frequently mutated sites were at A-T base pairs and accounted for more than one-third of all induced nonsense mutations. The two hottest sites were at the only occurrences of the 5'-TATA-3' tetranucleotide in lacI, a sequence expected to be a preferred binding site for a psoralen. Both A-T-to-T-A and A-T-to-C-G transversions were well induced by angelicin treatment, but the frequency of each transversion depended on the particular site. We also detected significant induction of transversion mutations at G-C sites. The induction of transversions by an SOS-dependent mutagen that generates lesions at pyrimidines supports the idea that DNA lesions influence the selection of bases that are incorporated via the process of SOS repair.
authors.forename: S S
authors.initials: SS
authors.lastname: Miller
authors.forename: E
authors.initials: E
authors.lastname: Eisenstadt
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics*; D011564:Furocoumarins / Q000633:toxicity*; D007763:Lac Operon; D009154:Mutation / Q000187:drug effects; D011743:Pyrimidines; D013014:SOS Response, Genetics
chemical_list: D004269:DNA, Bacterial; D011564:Furocoumarins; D011743:Pyrimidines; C011659:angelicin