Title
Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Department of Biochemistry and Molecular Pharmacology
Date
9-8-2005
Document Type
Article
Medical Subject Headings
Cisplatin; DNA Repair; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Escherichia coli; Genes, Bacterial; Methylnitronitrosoguanidine; Mutagens; *Mutation; Rifampin; Temperature
Disciplines
Life Sciences | Medicine and Health Sciences
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.
Rights and Permissions
Citation: Mutat Res. 2005 Oct 15;578(1-2):406-16. Link to article on publisher's site