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Nucleic Acids Research, 1988, Vol. 16, No. 3 1063-1078
© 1988


Articles

Induction of an abortive and futile DNA repair process in E.coli by the antitumor DNA bifunctional intercalator, ditercalinium: role in polA in death induction

Bernard Lambert, Bernard P. Roques1 and Jean-Bernard Le Pecq

Unité de Physicochimie Macromoléculaire, LA 147 CNRS et U 140 INSERM, Institut Gustave Roussy 94805 Villejuif Cédex 1Département de Chimie Organique, UA 498 CNRS et U 226 INSERM, UER des Sciences Pharmaceutiques et Biologiques 4 Avenue de I'Observatoire, 75006 Paris, France

Received December 4, 1987. Accepted January 8, 1988.

Ditercalinium, an antitumor bifunctional intercalator which forms a high affinity reversible complex with DNA, was found to be specifically cytotoxic for po1A and lig7 E. coil strains. In the po1A strain, the cytotoxic effect of ditercalinium was suppressed by the uvrA mutation. DNA single strand breaks accumulated in presence of ditercalinium at high temperature in lig7 strains but not in po1A strains. Ditercalinium caused no DNA synthesis inhibition although it was able to induce SOS functions. It is proposed that the ditercalinium DNA complex because of its non covalent nature acts as a dummny lesion for the UV repair system in E. coli leading to a futile and abortive repair process.

Polymerase I appears to be required to prevent the malfunctfoning of a DNA repair process triggered by molecules forming non covalent complex with DNA.


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