Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli
Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli
复制标题
DOI：
10.1073/pnas.131077798
复制
发表时间：
2001-06-19
影响因子：
11.1
通讯作者：
Wallace, SS
中科院分区：
文献类型：
--
作者：
Blaisdell, JO;Wallace, SS
据推测，电离辐射会产生一种独特的细胞DNA损伤形式，称为“簇状损伤”或“成倍损伤部位”。在这里，我们证明了聚集性DNA损伤确实是通过电离辐射在大肠杆菌中形成的，并在试图的碱基切除修复过程中转化为致命的双链断裂。在具有氧化DNA糖基酶的野生型细胞中，在可修复的单个损伤处裂解DNA，在辐射后孵育期间辐射诱导的簇处形成双链断裂，并且以剂量依赖的方式形成。缺乏这些酶的大肠杆菌突变体不会在辐射后形成双链断裂，而且比野生型细胞具有更强的辐射抗性。此外，在突变细胞中过量生产其中一种氧化DNA糖基酶会导致辐射敏感的表型和双链断裂数量的增加。因此，在评估辐射风险时，必须考虑氧化DNA糖基酶在增强DNA损伤方面的作用。
It has been postulated that ionizing radiation produces a unique form of cellular DNA damage called "clustered damages" or "multiply damaged sites". Here, we show that clustered DNA damages are indeed formed in Escherichia coli by ionizing radiation and are converted to lethal double-strand breaks during attempted base-excision repair. In wild-type cells possessing the oxidative DNA glycosylases that cleave DNA at repairable single damages, double-strand breaks are formed at radiation-induced clusters during postirradiation incubation and also in a dose-dependent fashion. E. coli mutants lacking these enzymes do not form double-strand breaks postirradiation and are substantially more radioresistant than wild-type cells. Furthermore, overproduction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand breaks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.