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.
Ditercalinium, an antitumor bifunctional intercalator which forms a high affinity reversible complex with DNA, was found to be specifically cytotoxic for polA and lig7 E. coli strains. In the polA 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 polA 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 dummy 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 malfunctioning of a DNA repair process triggered by molecules forming non covalent complex with DNA.
Lambert
B
B
Unité de Physicochimie Macromoléculaire, LA 147 CNRS, Villejuif, France.
Roques
B P
BP
Le Pecq
J B
JB
D001426:Bacterial Proteins / Q000235:genetics; D002227:Carbazoles / Q000494:pharmacology*; D004249:DNA Damage; D011088:DNA Ligases / Q000235:genetics; D004256:DNA Polymerase I / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000187:drug effects* / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D007364:Intercalating Agents / Q000494:pharmacology*; D008954:Models, Biological; D013014:SOS Response, Genetics / Q000187:drug effects*; D013696:Temperature
D001426:Bacterial Proteins; D002227:Carbazoles; D004269:DNA, Bacterial; D007364:Intercalating Agents; D004256:DNA Polymerase I; D011088:DNA Ligases; C042804:ditercalinium