Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Cisplatin; DNA Repair; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Escherichia coli; Genes, Bacterial; Methylnitronitrosoguanidine; Mutagens; *Mutation; Rifampin; Temperature
Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: Mutat Res. 2005 Oct 15;578(1-2):406-16. Link to article on publisher's site
DOI of Published Version
Calmann, Melissa A. and Marinus, Martin G., "Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli" (2005). GSBS Student Publications. 170.