title: Mutations in topA interfere with the inducible expression of DNA damage response loci in Salmonella typhimurium.
abstract: Strains of Salmonella typhimurium deficient in topoisomerase I activity (topA mutants) are UV sensitive and non-mutable (Overbye and Margolin: J Bacteriol 146:170-178, 1981). Using lac-operon fusions to DNA damage inducible (din) loci we investigated whether these observations could be explained by an inability of topA strains to efficiently induce DNA damage responses. Mitomycin C (MMC)-induced expression of lac-operon fusions to uvrB and to a second SOS locus, din-9, was largely eliminated in topA bacteria. The inducible expression of several other din-fusions was also diminished. This inducibility defect was mimicked by growth of din-9 topA+ bacteria in media of high osmolarity, a condition that leads to increased DNA supercoiling. Inhibitors of DNA gyrase efficiently induced din-9 in topA bacteria. Together, these results suggest that the topA effect on din expression may be mediated at the level of DNA supercoiling. The sensitivities of a number of din-fusions to topA paralleled the degree to which they were repressed by excess LexA, suggesting that mutations in topA might influence LexA-operator interactions and/or increase lexA expression.
authors.affiliation: Laboratory of Toxicology, Harvard University School of Public Health, Boston, MA 02115.
authors.forename: C M
authors.initials: CM
authors.lastname: Smith
authors.forename: Z
authors.initials: Z
authors.lastname: Arany
authors.forename: C
authors.initials: C
authors.lastname: Orrego
authors.forename: E
authors.initials: E
authors.lastname: Eisenstadt
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases; D004264:DNA Topoisomerases, Type I / Q000235:genetics* / Q000378:metabolism; D004278:DNA, Superhelical / Q000378:metabolism; D029968:Escherichia coli Proteins; D007700:Kinetics; D007763:Lac Operon; D009154:Mutation; D009994:Osmolar Concentration; D013014:SOS Response, Genetics / Q000235:genetics*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D001426:Bacterial Proteins; D004278:DNA, Superhelical; D029968:Escherichia coli Proteins; C058093:UvrB protein, E coli; D004265:DNA Helicases; D004264:DNA Topoisomerases, Type I