Traceless Tandem Lesion Formation in DNA from a Nitrogen-Centered Purine Radical.

ABSTRACT: Nitrogen-centered nucleoside radicals are commonly produced reactive intermediates in DNA exposed to γ-radiolysis and oxidants, but their reactivity is not well understood. Examination of the reactivity of independently generated 2'-deoxyadenosin- N6-yl radical (dA•) reveals that it is an initiator of tandem lesions, an important form of DNA damage that is a hallmark of γ-radiolysis. dA• yields O₂-dependent tandem lesions by abstracting a hydrogen atom from the C5-methyl group of a 5'-adjacent thymidine to form 5-(2'-deoxyuridinyl)methyl radical (T•). The subsequently formed thymidine peroxyl radical adds to the 5'-adjacent dG, ultimately producing a 5'-OxodGuo-fdU tandem lesion. Importantly, the initial hydrogen abstraction repairs dA• to form dA. Thus, the involvement of dA• i

SUBMITTER: Zheng L 

PROVIDER: S-EPMC5966344 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature