Frameshift lesions induced by oxazolopyridocarbazoles are recognized by the mismatch repair system in Escherichia coli.
The simple reversible intercalating agent isopropyl-OPC (iPr-OPC) induces frameshift-1 mutations in Salmonella typhimurium and Escherichia coli. The mutagenic responses of S. typhimurium and E. coli wild-type strains are not proportional to the amount of drug intercalated into double-stranded nucleic acids in living bacteria; it occurs only above a minimum level of binding. The fact that mismatch-repair-deficient (mutS) as well as adenine-methylation-deficient (dam) E. coli mutants are hypermutable at low concentrations of iPr-OPC suggests that the majority of mutants induced by this intercalating drug occur as mismatch-repairable mutations (or lesions) in the newly synthesized DNA strand close to the replication fork.
René
B
B
Laboratoire de Biochimie-Enzymologie, INSERM U140, CNRS UA147, Institut Gustave Roussy, Villejuif, France.
Auclair
C
C
Paoletti
C
C
D000470:Alkaloids / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D004249:DNA Damage; D004260:DNA Repair; D004269:DNA, Bacterial / Q000187:drug effects* / Q000235:genetics; D004611:Ellipticines / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics / Q000502:physiology; D009154:Mutation; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)
D000470:Alkaloids; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D004611:Ellipticines; C049828:2-isopropyl-7,10,12-trimethyl-6H-(1,3)oxazolo(5,4c)pyrido(3,4-g)carbazole; D008780:Methyltransferases; D015265:Site-Specific DNA-Methyltransferase (Adenine-Specific)