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Comparative Study
. 2005 Oct 15;578(1-2):406-16.
doi: 10.1016/j.mrfmmm.2005.06.030.

Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli

Melissa A Calmann  1 , M G Marinus
Affiliations
Comparative Study

Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli

Melissa A Calmann et al. Mutat Res. .

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.

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Figures

Fig. 1
Fig. 1
Survival at 30°C of wildtype (CR34), dnaE486 (JW130), dam-13 (GM2927) and dam-13 dnaE486 (GM8096) strains after treatment with cisplatin and MNNG.
Fig. 2
Fig. 2
Survival of strains GM8051 (dnaX36) at 30°C and 37°C, GM2927 (dam-13) at 37°C, GM8128 (pdnaX+/dnaX36) at 30°C and GM8137 (pdnaX+/AB1157) at 30°C after treatment with cisplatin and MNNG.
Fig. 3
Fig. 3
Survival at 30°C of wildtype (AB1157), dnaN159 (GM8020), dam-13 (GM2927), dam-13 dnaN159 (GM8024) and dam-13 dnaN159 mutS458 (GM8060) strains after treatment with cisplatin and MNNG.
Fig. 4
Fig. 4
Survival at 30°C of wildtype (CR34), dnaG3 (JW177), dam-13 (GM2927) and dam-13 dnaG3 (GM8047) strains after treatment with cisplatin and MNNG.
Fig. 5
Fig. 5
Survival at 30°C of wildtype (AB1157), dnaB43 (GM534), dam-13 (GM2927) and dam-13 dnaB43 (GM8026) strains after treatment with cisplatin and MNNG.
Fig. 6
Fig. 6
Reversion of lacZ alleles in CC101–CC107 (top row), and their dnaN159 (middle row) and mutS215 (bottom row) derivatives.
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