INFLUENCE OF DNA SUPERCOILING ON CISPLATIN TOXICITY IN ESCHERICHIA-COLI K-12

DNA supercoiling is known to modulate the activity of numerous promote rs in vitro and in vivo. Moreover, it has been reported to modulate th e 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 decr ease of about 25% in superhelical density were studied. Mutant strains gyrA(224) and gyrB(225) showed abolished sensitivity to CDDP as the p arental strain while the grypB(226) mutant was resistant. This resista nt was abolished in uvrA (excision-repair) and recA (recombination and SOS processes) mutant derivatives. Thus supercoiling might play a rol e as an indirect modulator of CDDP toxicity in bacteria by interfering with repair processes.