DNA strand breaks induced by concerted interaction of H radicals and
low-energy electrons |
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Authors: | I?D?bkowska J?Rak Email author" target="_blank">M?GutowskiEmail author |
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Institution: | 1.Chemical Sciences Division,Pacific Northwest National Laboratory,Richland,USA;2.Department of Chemistry,University of Gdańsk,Gdańsk,Poland;3.Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,Prague 6,Czech Republic |
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Abstract: | We propose a mechanism of DNA single strand breaks
induced by low-energy electrons. Density functional theory calculations have
been performed on a neutral, hydrogenated, and/or negatively charged
nucleotide of cytosine in the gas phase to identify barriers for the
phosphate-sugar O–C bond cleavage. Attachment of the first excess electron
induces intermolecular proton transfer to cytosine. The resulting neutral
radical of hydrogenated cytosine binds another excess electron, and the
excess charge is localized primarily on the C6 atom. A barrier encountered
for proton transfer from the C2’ atom of the adjacent sugar unit to the C6
atom of cytosine is 3.6 and 5.0 kcal/mol, based on the MPW1K and B3LYP
electronic energies corrected for zero-point vibrations, respectively. The
proton transfer is followed by a barrier-free sugar-phosphate C–O bond
cleavage. The proton transfer is impossible for the neutral nucleotide, as
there is no local minimum for the product. In the case of anionic and
hydrogenated nucleotides the same barrier determined at the B3LYP level is
as large as 29.3 and 22.4 kcal/mol respectively. This illustrates that the
consecutive hydrogenation and electron attachment make the nucleotide of
cytosine susceptible to a strand break. The rate of the C–O bond cleavage in
the anion of hydrogenated nucleotide of cytosine is estimated to be ca.
1010 s-1. The proposed mechanism proceeds through bound anionic
states, not through metastable states with finite lifetimes and discrete
energy positions with respect to the neutral target. The results suggest
that
at least for DNA without hydration
even very low-energy electrons may cleave the DNA backbone. |
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Keywords: | |
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