Schaaper R M, Dunn R L
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Mutat Res. 1998 Jun 18;402(1-2):23-8. doi: 10.1016/s0027-5107(97)00278-9.
Previous studies in our laboratory have identified a set of mutations in the Escherichia coli dnaE gene that confer increased accuracy of DNA replication (antimutators). The dnaE gene encodes the polymerase subunit of DNA polymerase III holoenzyme that replicates the E. coli chromosome. Here, we have investigated their effect on mutagenesis by the base analog N4-aminocytidine (4AC). For three different mutational markers, rifampicin resistance, nalidixic acid resistance and lacI forward mutagenesis, the dnaE911 allele reduced 4AC-induced mutagenesis by approximately 2.5-fold, while the dnaE915 allele reduced it by 2.5-, 3.5- and 6.5-fold, respectively. We also investigated the dependence of 4AC mutagenesis on mutations in the MutHLS mismatch repair system and the UvrABC nucleotide excision repair system. The results show that mutagenesis by 4AC is unaffected by defects in either system. The combined results point to the critical role of the DNA polymerase in preventing mutations by base analogs.
我们实验室之前的研究在大肠杆菌dnaE基因中鉴定出了一组突变，这些突变可提高DNA复制的准确性（抗突变体）。dnaE基因编码负责复制大肠杆菌染色体的DNA聚合酶III全酶的聚合酶亚基。在此，我们研究了它们对碱基类似物N4-氨基胞苷（4AC）诱变作用的影响。对于三种不同的突变标记，即利福平抗性、萘啶酸抗性和lacI正向诱变，dnaE911等位基因使4AC诱导的诱变作用降低了约2.5倍，而dnaE915等位基因分别使其降低了2.5倍、3.5倍和6.5倍。我们还研究了4AC诱变对MutHLS错配修复系统和UvrABC核苷酸切除修复系统中突变的依赖性。结果表明，4AC诱变不受任一系统缺陷的影响。综合结果表明，DNA聚合酶在防止碱基类似物引起的突变中起关键作用。
