Much of spontaneous mutagenesis in Escherichia coli is due to error-prone DNA repair: implications for spontaneous carcinogenesis.
Much of spontaneous mutagenesis in Escherichia coli is due to error-prone DNA repair: implications for spontaneous carcinogenesis.
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大肠杆菌中的大部分自发突变是由于容易出错的 DNA 修复造成的：对自发致癌的影响。
DOI：
10.1093/carcin/2.9.863
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发表时间：
1981
期刊：
影响因子：
4.7
通讯作者：
Smith,KC
中科院分区：
文献类型：
--
作者：
Sargentini,NJ;Smith,KC
本文研究了大肠杆菌中DNA修复基因uvrA、uvrB、uvrD、recA、recB、莱克萨和umuC在自发突变中的作用。测定了UAA（his-4和trpE 65）、UAG（lacZ 53）和移码（trpE 9777）突变的回复突变以及发生缬氨酸抗性的正向突变的每种细菌/细胞分裂的自发突变率（μ）。丰富的生长培养基增加了野生型菌株的μ，但在auvrB 5菌株中没有。在基本生长培养基中，uvrA和duvrB菌株具有最大的μ（比同基因野生型菌株大1.9-6.2倍，取决于突变测定）。携带lexA、recA、umuC或两种uvr和drec B突变（组合）的uvr B菌株，即，抑制易错DNA修复的突变的μ值最低（比uvrB菌株低10倍）。recA和lexA突变也使uvr+菌株的μ降低了约2倍。自发诱变的易错修复依赖性区段的遗传控制显示出与u. v.辐射诱变的遗传控制定性相似。突变，这大大减少了自发突变，没有影响遗传重组。有人提出，在recA、莱克萨、umuC和uvrD recB菌株中观察到的低水平自发突变是由于DNA复制过程中产生的错误，而在野生型，特别是uvrA和uvrB菌株中观察到的增强水平的自发突变是由于正常代谢反应在DNA中产生的可切除损伤，并且这种未切除的损伤通过易错DNA修复诱导突变。这些结果进行了讨论，其相关性自发性癌变。
The role of DNA repair genes (uvrA, uvrB, uvrD, recA, recB, lexA,andumuC) in spontaneous mutagenesis was examined inEscherichia coli. The spontaneous mutation rate per bacterium per cell division (μ) was determined for the reversion of UAA (his-4andtrpE65), UAG (lacZ53), and frameshift (trpE9777) mutations, and for the occurrence of forward mutations to valine resistance. Rich growth medium enhanced μ in a wild-type strain but not in auvrB5strain. In minimal growth medium, theuvrAanduvrBstrains had the largest μ (1.9–6.2-fold greater than that for isogenic wild-type strains, depending on the mutation assay). TheuvrBstrains carryinglexA, recA, umuC,or both theuvrDandrec Bmutations (in combination), i.e., mutations that inhibit error-prone DNA repair, had the lowest μ values (˜10-fold less than theuvrBstrain). TherecAandlexAmutations also reduced μ (by ˜ 2-fold) inuvr+strains. The genetic control of the error prone repair-dependent sector of spontaneous mutagenesis was shown to be qualitatively similar to the genetic control for u.v. radiation mutagenesis. TheumuCmutation, which drastically reduced spontaneous mutagenesis, had no effect on genetic recombination. It is proposed that the low level of spontaneous mutagenesis observed in therecA, lexA, umuC,and theuvrD recBstrains is due to errors made during DNA replication, while the enhanced level of spontaneous mutagenesis observed in the wild type, and especially in theuvrAanduvrBstrains, is due to excisable lesions that are produced in the DNA by normal metabolic reactions, and that such unexcised lesions induce mutations via error-prone DNA repair. These results are discussed in terms of their relevance to spontaneous carcinogenesis.