Influence of DNA supercoiling on cisplatin toxicity in Escherichia coli K-12.
DNA supercoiling is known to modulate the activity of numerous promoters in vitro and in vivo. Moreover, it has been reported to modulate the rate of formation of cisplatin/DNA crosslinks in vitro. In order to address the question of how the topology influences CDDP toxicity in E. coli, three mutants with altered gyrase activity which led to a decrease of about 25% in superhelical density were studied. Mutant strains gyrA224 and gyrB225 showed similar sensitivity to CDDP as the parental strain while the gyrB226 mutant was resistant. This resistance was abolished in uvrA (excision-repair) and recA (recombination and SOS processes) mutant derivatives. Thus supercoiling might play a role as an indirect modulator of CDDP toxicity in bacteria by interfering with repair processes.
Bouayadi
K
K
Laboratoire de Pharmacologie et Toxicologie Fondamentales du CNRS, Toulouse, France.
Salles
B
B
D000251:Adenosine Triphosphatases / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D018736:DNA Adducts; D004260:DNA Repair; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry*; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins / Q000235:genetics; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins; D009154:Mutation; D011938:Rec A Recombinases / Q000235:genetics
D001426:Bacterial Proteins; D018736:DNA Adducts; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C057270:cisplatin-DNA adduct; D011938:Rec A Recombinases; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D004250:DNA Topoisomerases, Type II; D002945:Cisplatin