Suppressible base substitution mutations induced by angelicin (isopsoralen) in the Escherichia coli lacI gene: implications for the mechanism of SOS mutagenesis

J Bacteriol. 1987 Jun;169(6):2724-9. doi: 10.1128/jb.169.6.2724-2729.1987.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • DNA Damage*
  • DNA Repair*
  • DNA Replication
  • DNA, Bacterial / genetics*
  • Escherichia coli / genetics*
  • Furocoumarins / toxicity*
  • Lac Operon
  • Mutation / drug effects
  • Pyrimidines
  • SOS Response, Genetics*

Substances

  • DNA, Bacterial
  • Furocoumarins
  • Pyrimidines
  • angelicin