顺铂和N-甲基-N'-硝基-N-亚硝基胍对大肠杆菌DNA突变体的不同影响。
Differential effects of cisplatin and MNNG on dna mutants of Escherichia coli.
作者信息
Calmann Melissa A, Marinus M G
机构信息
Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605, USA.
出版信息
Mutat Res. 2005 Oct 15;578(1-2):406-16. doi: 10.1016/j.mrfmmm.2005.06.030.
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.
哺乳动物细胞或大肠杆菌dam突变体中的DNA错配修复（MMR）增强了顺铂和N-甲基-N'-硝基-N-亚硝基胍（MNNG）的细胞毒性作用。我们发现，与野生型不同，dnaE486（DNA聚合酶III全酶的α催化亚基）突变体和DnaX（钳位装载亚基）过量产生菌在允许生长的温度下对顺铂敏感，但对MNNG有抗性。dam-13 dnaN159（β滑动钳）细菌对顺铂的存活率明显低于dam细胞，提示MMR降低，这可能是由于MutS-β钳相互作用减少所致。我们还发现，dnaE486（10倍）、dnaN159（35倍）和dnaX36（10倍）菌株中对利福平耐药的自发突变频率升高。dnaN159菌株中的突变谱与SOS诱导增加一致，并非MMR缺陷的指示。
Zotero 插件