title: Chromosomally encoded gyrase inhibitor GyrI protects Escherichia coli against DNA-damaging agents.
abstract: DNA gyrase, a type II topoisomerase, is the sole supercoiling activity in the cell and is essential for cell survival. There are two proteinaceous inhibitors of DNA gyrase that are plasmid-borne and ensure maintenance of the plasmids in bacterial populations. However, the physiological role of GyrI, an inhibitor of DNA gyrase encoded by the Escherichia coli genome, has been elusive. Previously, we have shown that GyrI imparts resistance against microcin B17 and CcdB. Here, we find that GyrI provided partial/limited protection against the quinolone class of gyrase inhibitors but had no effect on inhibitors that interfere with the ATPase activity of the enzyme. Moreover, GyrI negated the effect of alkylating agents, such as mitomycin C and N-methyl- N-nitro- N-nitrosoguanidine, that act independently of DNA gyrase. Hence, in vivo, GyrI appears to be involved in reducing DNA damage from many sources. In contrast, GyrI is not effective against lesions induced by ultraviolet radiation. Furthermore, the expression of GyrI does not significantly alter the topology of DNA. Thus, although isolated as an inhibitor of DNA gyrase, GyrI seems to have a broader role in vivo than previously envisaged.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology; D002939:Ciprofloxacin / Q000494:pharmacology; D004249:DNA Damage; D004269:DNA, Bacterial / Q000187:drug effects*; D004278:DNA, Superhelical / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000502:physiology*; D005798:Genes, Bacterial; D017930:Genes, Reporter; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D016296:Mutagenesis; D009268:Nalidixic Acid / Q000494:pharmacology; D010957:Plasmids; D015363:Quinolones / Q000494:pharmacology; D012097:Repressor Proteins / Q000502:physiology*; D013014:SOS Response, Genetics; D059005:Topoisomerase II Inhibitors; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D004269:DNA, Bacterial; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D015363:Quinolones; D012097:Repressor Proteins; C110533:SbmC protein, E coli; D059005:Topoisomerase II Inhibitors; D008769:Methylnitronitrosoguanidine; D009268:Nalidixic Acid; D016685:Mitomycin; D002939:Ciprofloxacin; D001616:beta-Galactosidase