Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli

It has been postulated that ionizing radiation produces a unique form of ce llular DNA damage called "clustered damages" or "multiply damaged sites". H ere, we show that clustered DNA damages are indeed formed in Escherichia co li by ionizing radiation and are converted to lethal double-strand breaks d uring attempted base-excision repair. In wild-type cells possessing the oxi dative DNA glycosylases that cleave DNA at repairable single damages, doubl e-strand breaks are formed at radiation-induced clusters during postirradia tion incubation and also in a dose-dependent fashion. E. coli mutants lacki ng these enzymes do not form double-strand breaks postirradiation and are s ubstantially more radioresistant than wild-type cells. Furthermore, overpro duction of one of the oxidative DNA glycosylases in mutant cells confers a radiosensitive phenotype and an increase in the number of double-strand bre aks. Thus, the effect of the oxidative DNA glycosylases in potentiating DNA damage must be considered when estimating radiation risk.