TY - JOUR
T1 - DNA Damage Emanating from a Neutral Purine Radical Reveals the Sequence Dependent Convergence of the Direct and Indirect Effects of γ-Radiolysis
AU - Zheng, Liwei
AU - Greenberg, Marc M.
N1 - Funding Information:
We are grateful for generous financial support from the National Institute of General Medical Science (GM-054996). L.Z. thanks Johns Hopkins University for the Glen E. Meyer ’39 Fellowship. We thank M. Sevilla and A. Adhikary for helpful discussions.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/12/13
Y1 - 2017/12/13
N2 - 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.
AB - 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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U2 - 10.1021/jacs.7b10942
DO - 10.1021/jacs.7b10942
M3 - Article
C2 - 29190086
AN - SCOPUS:85038219328
SN - 0002-7863
VL - 139
SP - 17751
EP - 17754
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 49
ER -