Jo. Blaisdell et Ss. Wallace, Abortive base-excision repair of radiation-induced clustered DNA lesions in Escherichia coli, P NAS US, 98(13), 2001, pp. 7426-7430
Citations number
44
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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.