Spontaneous mutagenesis associated with nucleotide excision repair in Escherichia coli
Spontaneous mutagenesis associated with nucleotide excision repair in Escherichia coli
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DOI：
10.1111/j.1365-2443.2008.01185.x
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发表时间：
2008-05-01
期刊：
影响因子：
2.1
通讯作者：
Maki, Hisaji
中科院分区：
文献类型：
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作者：
Hasegawa, Kimiko;Yoshiyama, Kaoru;Maki, Hisaji
大肠杆菌中发生的绝大多数自发突变被认为来自自发DNA损伤，包括氧化碱基损伤。去除内在诱变剂和修复DNA损伤的系统有助于抑制自发突变。核苷酸切除修复（NER）是一种通用的DNA修复系统，可以消除DNA上的各种损伤。因此，我们预测，NER可能参与抑制自发突变，并分析了碱基替换内的nER熟练（野生型），缺乏和过量生产E.大肠杆菌菌株。令人惊讶的是，突变频率在NER缺陷型菌株中较低，而在NER过量生产型菌株中较高，而不是在NER精通型菌株中。这些结果表明，自相矛盾的是，NER有助于产生自发突变，而不是在正常生长条件下抑制，转录偶联修复也参与了这一过程。使用大肠携带编辑核酸外切酶缺陷型polA突变的大肠杆菌菌株，我们进一步获得的数据表明，不必要的NER可能解释了这些发现，因此，在DNA聚合酶I修复DNA合成过程中引入的错误将导致不必要的碱基取代。因此，修复系统本身可能是自发突变的重要发生器。
The vast majority of spontaneous mutations occurring in Escherichia coli are thought to be derived from spontaneous DNA lesions, which include oxidative base damage. Systems for removing intrinsic mutagens and repairing DNA lesions contribute to the suppression of spontaneous mutations. Nucleotide excision repair (NER) is a general DNA repair system that eliminates various kinds of lesions from DNA. We therefore predicted that NER might be involved in suppression of spontaneous mutations, and analyzed base substitutions occurring spontaneously within the rpoB gene in NER-proficient (wild-type), -deficient and -overproducing E. coli strains. Surprisingly, the mutation frequency was lower in NER-deficient strains, and higher in NER-overproducing strains, than in the NER-proficient strain. These results suggest, paradoxically, that NER contributes to the generation of spontaneous mutation rather than to its suppression under normal growth conditions, and that transcription-coupled repair also participates in this process. Using E. coli strains that carried an editing exonuclease-deficient polA mutation, we further obtained data suggesting that unnecessary NER might account for these findings, so that errors introduced during repair DNA synthesis by DNA polymerase I would result in unwanted base substitutions. The repair system itself may thus be an important generator of spontaneous mutation.