Hersh Megan N, Morales Liza D, Ross Kimberly J, Rosenberg Susan M
Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030-3411, USA.
J Bacteriol. 2006 Apr;188(7):2336-42. doi: 10.1128/JB.188.7.2336-2342.2006.
Escherichia coli strains carrying null alleles of genes encoding single-strand-specific exonucleases ExoI and ExoVII display elevated frameshift mutation rates but not base substitution mutation rates. We characterized increased spontaneous frameshift mutation in ExoI- ExoVII- cells and report that some of this effect requires RecA, an inducible SOS DNA damage response, and the low-fidelity, SOS-induced DNA polymerase DinB/PolIV, which makes frameshift mutations preferentially. We also find that SOS is induced in ExoI- ExoVII- cells. The data imply a role for the single-stranded exonucleases in guarding the genome against mutagenesis by removing excess single-stranded DNA that, if left, leads to SOS induction and PolIV-dependent mutagenesis. Previous results implicated PolIV in E. coli mutagenesis specifically during starvation or antibiotic stresses. Our data imply that PolIV can also promote mutation in growing cells under genome stress due to excess single-stranded DNA.
携带编码单链特异性核酸外切酶ExoI和ExoVII的基因无效等位基因的大肠杆菌菌株表现出较高的移码突变率,但碱基替换突变率并未升高。我们对ExoI-ExoVII-细胞中自发移码突变增加的情况进行了表征,并报告称这种效应部分需要RecA、一种可诱导的SOS DNA损伤反应以及低保真度的、SOS诱导的DNA聚合酶DinB/PolIV,后者优先导致移码突变。我们还发现ExoI-ExoVII-细胞中会诱导SOS。这些数据表明,单链核酸外切酶通过去除多余的单链DNA来保护基因组免受诱变,否则这些单链DNA会导致SOS诱导和PolIV依赖性诱变。先前的结果表明,PolIV在大肠杆菌诱变中发挥作用,特别是在饥饿或抗生素应激期间。我们的数据表明,由于存在过量的单链DNA,在基因组应激条件下,PolIV也可以促进生长中的细胞发生突变。