title: Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli.
abstract: DNA mismatch repair (MMR) in mammalian cells or Escherichia coli dam mutants increases the cytotoxic effects of cisplatin and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). We found that, unlike wildtype, the dnaE486 (alpha catalytic subunit of DNA polymerase III holoenzyme) mutant, and a DnaX (clamp loader subunits) over-producer, are sensitive to cisplatin but resistant to MNNG at the permissive temperature for growth. Survival of dam-13 dnaN159 (beta sliding clamp) bacteria to cisplatin was significantly less than dam cells, suggesting decreased MMR, which may be due to reduced MutS-beta clamp interaction. We also found an elevated spontaneous mutant frequency to rifampicin resistance in dnaE486 (10-fold), dnaN159 (35-fold) and dnaX36 (10-fold) strains. The mutation spectrum in the dnaN159 strain was consistent with increased SOS induction and not indicative of MMR deficiency.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Calmann
authors.forename: M G
authors.initials: MG
authors.lastname: Marinus
mesh_terms: D002945:Cisplatin / Q000633:toxicity*; D004260:DNA Repair; D004269:DNA, Bacterial / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D005798:Genes, Bacterial; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D012293:Rifampin / Q000633:toxicity; D013696:Temperature
chemical_list: D004269:DNA, Bacterial; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D002945:Cisplatin; D012293:Rifampin