New complexities of SOS-induced "untargeted" mutagenesis in Escherichia coli as revealed by mutation accumulation and whole-genome sequencing.

New complexities of SOS-induced "untargeted" mutagenesis in Escherichia coli as revealed by mutation accumulation and whole-genome sequencing. DNA Repair (Amst). 2020 Apr 18;90:102852 Authors: Niccum BA, Coplen CP, Lee H, Mohammed Ismail W, Tang H, Foster PL Abstract 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 ...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research