Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli
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UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyGraduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2005-09-08Keywords
Cisplatin; DNA Repair; DNA, Bacterial; Dose-Response Relationship, Drug; Drug Resistance, Microbial; Escherichia coli; Genes, Bacterial; Methylnitronitrosoguanidine; Mutagens; *Mutation; Rifampin; TemperatureLife Sciences
Medicine and Health Sciences
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Show full item recordAbstract
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.Source
Mutat Res. 2005 Oct 15;578(1-2):406-16. Link to article on publisher's siteDOI
10.1016/j.mrfmmm.2005.06.030Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33160PubMed ID
16144703Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.mrfmmm.2005.06.030