The mechanism of sensitivity to phleomycin in growing Escherichia coli cells.
Stationary-phase Escherichia coli B cells transferred to new growth medium are initially resistant to net DNA breakage by low concentrations of phleomycin, and become sensitive as DNA replication commences. From studies with inhibitors of various stages of the DNA replication cycle it is evident that it is not DNA synthesis itself that is required for induction of DNA breakage by phleomycin, but events associated with the initiation of DNA replication. Termination of replication in the absence of further initiaiton results in resistance to phleomycin. The cellular change responsible for changes in sensitivity to phleomycin could be the attachment of the bacterial chromosome to the cell membrane at initiation and detachment on termination of replication, suggesting an alteration in the balance between cellular DNA breakage and repair processes for membrane-associated compared with non-membrane-associated DNA.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D002701:Chloramphenicol / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004269:DNA, Bacterial / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004926:Escherichia coli / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects; D010626:Phenylethyl Alcohol / Q000494:pharmacology; D010692:Phleomycins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000096:biosynthesis; D012293:Rifampin / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013941:Thymine / Q000494:pharmacology; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010692:Phleomycins; D012329:RNA, Bacterial; D003561:Cytarabine; D002701:Chloramphenicol; D014364:Tryptophan; D010626:Phenylethyl Alcohol; D013941:Thymine; D013936:Thymidine; D012293:Rifampin; D006918:Hydroxyurea