When its DNA is damaged, Escherichia coli induces the SOS response, which consists of about 40 genes that encode activities to repair or tolerate the damage. Certain alleles of the major SOS-control genes, recA and lexA, cause constitutive expression of the response, resulting in an increase in spontaneous mutations. These mutations, historically called "untargeted", have been the subject of many previous studies. Here we re-examine SOS-induced mutagenesis using mutation accumulation followed by whole-genome sequencing (MA/WGS), which allows a detailed picture of the types of mutations induced as well as their sequence-specificity. Our results confirm previous findings that SOS expression specifically induces transversion base-pair substitutions, with rates averaging about 60-fold above wild-type levels. Surprisingly, the rates of G:C to C:G transversions, normally an extremely rare mutation, were induced an average of 160-fold above wild-type levels. The SOS-induced transversion showed strong sequence specificity, the most extreme of which was the G:C to C:G transversions, 60% of which occurred at the middle base of 5'GGC3'+5'GCC3' sites, although these sites represent only 8% of the G:C base pairs in the genome. SOS-induced transversions were also DNA strand-biased, occurring, on average, 2- to 4- times more often when the purine was on the leading-strand template and the pyrimidine on the lagging-strand template than in the opposite orientation. However, the strand bias was also sequence specific, and even of reverse orientation at some sites. By eliminating constraints on the mutations that can be recovered, the MA/WGS protocol revealed new complexities of SOS "untargeted" mutations.

中文翻译：

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突变积累和全基因组测序揭示了SOS诱导的大肠杆菌“非靶向”诱变的新复杂性。

当其DNA受损时，大肠杆菌会诱导SOS反应，该反应由约40个基因组成，这些基因编码修复或耐受该损伤的活性。主要SOS控制基因的某些等位基因recA和lexA引起反应的组成型表达，导致自发突变增加。这些突变在历史上被称为“非靶向”，已成为许多先前研究的主题。在这里，我们使用突变积累和全基因组测序（MA / WGS）重新检查SOS诱导的诱变，从而可以详细了解诱导的突变类型及其序列特异性。我们的结果证实了先前的发现，即SOS表达特异性诱导颠覆碱基对取代，其速率平均比野生型水平高约60倍。出人意料的是，G的比率：从C到C：G的转化，通常是极为罕见的突变，被诱导出平均比野生型水平高160倍。SOS诱导的转化表现出很强的序列特异性，其中最极端的是G：C到C：G的转化，其中60％发生在5'GGC3'+ 5'GCC3'位点的中间碱基仅代表基因组中G：C碱基对的8％。SOS诱导的颠换也是DNA链偏向的，当嘌呤在前导链模板上而嘧啶在滞后链模板上时，其发生频率平均比相反方向高2至4倍。但是，链偏向也是序列特异性的，甚至在某些位点具有反向取向。通过消除对可恢复突变的限制，