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DNA Damage Emanating From a Neutral Purine Radical Reveals the Sequence Dependent Convergence of the Direct and Indirect Effects of γ‑Radiolysis

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journal contribution
posted on 2017-11-30, 20:35 authored by Liwei Zheng, Marc M. Greenberg
Nucleobase radicals are the major intermediates generated by the direct (e.g., dA•+) and indirect (e.g., dA•) effects of γ-radiolysis. dA• was independently generated in DNA for the first time. The dA•+/dA• equilibrium, and consequently the reactivity in DNA, is significantly shifted toward the radical cation by a flanking dA. Tandem lesions emanating from dA• are the major products when the reactive intermediate is flanked by a 5′-dGT. In contrast, when dA• is flanked by dA, the increased dA•+ pKa results in DNA damage arising from hole transfer. This is the first demonstration that sequence effects lead to the intersection of the direct and indirect effects of ionizing radiation.

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