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.

作者：Jóhannes, Reynisson

来源：World journal of clinical oncology 2010 年 1卷 1期