Frameshift mutagenesis in Escherichia coli by reversible DNA intercalators: sequence specificity.
The mutagenic potency of the simple reversible intercalators isopropyl-OPC (iPr-OPC) and 9-aminoacridine (9-AA) is assessed in E. coli using reversion assays based on plasmids derived from pBR322 carrying various frameshift mutations within the tetracycline resistance gene in repetitive sequences: +/- 2 frameshift mutations within alternating GC sequences; +/- 1 frameshift mutation at runs of guanines. The results obtained show that iPr-OPC and 9-AA have a sequence specificity for mutagenesis: they revert +1 and -1 frameshift mutations within runs of monotonous G:C base pairs. The precise determination of the size of a small restriction fragment which contains the mutation allowed us to demonstrate that reversion occurred by -1 deletions for the +1 frameshift mutations and by +1 additions for the -1 frameshift mutations. The possible relations of this specific reversion with the base sequence specificity of the mutagenesis are briefly discussed.
René
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B
Laboratoire de Biochimie-Enzymologie, INSERM U 140, CNRS LA 147, Institut Gustave Roussy, Villejuif, France.
Auclair
C
C
Fuchs
R P
RP
Paoletti
C
C
D000470:Alkaloids / Q000494:pharmacology*; D000585:Aminacrine / Q000494:pharmacology*; D000609:Aminoacridines / Q000494:pharmacology*; D001483:Base Sequence; D004269:DNA, Bacterial / Q000235:genetics; D004611:Ellipticines / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D007364:Intercalating Agents / Q000494:pharmacology*; D009154:Mutation / Q000187:drug effects*; D010957:Plasmids; D013329:Structure-Activity Relationship; D013752:Tetracycline
D000470:Alkaloids; D000609:Aminoacridines; D004269:DNA, Bacterial; D004611:Ellipticines; D007364:Intercalating Agents; C049828:2-isopropyl-7,10,12-trimethyl-6H-(1,3)oxazolo(5,4c)pyrido(3,4-g)carbazole; D000585:Aminacrine; D013752:Tetracycline