ArticleWorld journal of clinical oncology2010
Molecular mechanism of base pairing infidelity during DNA duplication upon one-electron oxidation.
Article in World journal of clinical oncology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The guanine radical cation (G(•+)) is formed by one-electron oxidation from its parent guanine (G). G(•+) is rapidly deprotonated in the aqueous phase resulting in the formation of the neutral guanine radical [G(-H)(•)]. The loss of proton occurs at the N1 nitrogen, which is involved in the classical Watson-Crick base pairing with cytosine (C). Employing the density functional theory (DFT), it has been observed that a new shifted base pairing configuration is formed between G(-H)(•) and C constituting only two hydrogen bonds after deprotonation occurs. Using the DFT method, G(-H)(•) was paired with thymine (T), adenine (A) and G revealing substantial binding energies comparable to those of classical G-C and A-T base pairs. Hence, G(-H)(•) does not display any particular specificity for C compared to the other bases. Taking into account the long lifetime of the G(-H)(•) radical in the DNA helix (5 s) and the rapid duplication rate of DNA during mitosis/meiosis (5-500 bases per s), G(-H)(•) can pair promiscuously leading to errors in the duplication process. This scenario constitutes a new mechanism which explains how one-electron oxidation of the DNA double helix can lead to mutations.
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