title: Molecular mechanism of base pairing infidelity during DNA duplication upon one-electron oxidation.
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.
authors: Jóhannes Reynisson, Department of Chemistry and Auckland Bioengineering Institute, The University of Auckland, Auckland 1142, New Zealand.
authors: Jóhannes
authors: J
authors: Reynisson
references: Phys Chem Chem Phys. 2010 Aug 21;12(31):9088-93
references: 20532316
references: Nature. 2000 Feb 24;403(6772):859-66
references: 10706276
references: Aging Cell. 2004 Feb;3(1):7-12
references: 14965349
references: Biochemistry. 1995 Apr 18;34(15):5003-10
references: 7711022
references: Eur J Pharmacol. 2009 Dec 25;625(1-3):143-50
references: 19836377
references: Acc Chem Res. 2000 Apr;33(4):253-60
references: 10775318
references: Cell Res. 2008 Jan;18(1):148-61
references: 18166979
references: Free Radic Res Commun. 1992;16(6):349-79
references: 1325399
references: J Am Chem Soc. 2006 Dec 20;128(50):15966-7
references: 17165712
references: Chem Res Toxicol. 1989 Nov-Dec;2(6):416-22
references: 2519731
references: Biol Chem. 1997 Nov;378(11):1293-7
references: 9426189
references: Proc Natl Acad Sci U S A. 2005 May 10;102(19):6698-703
references: 15814617
references: Mol Cell. 2010 Feb 12;37(3):311-20
references: 20159551
references: Acc Chem Res. 2000 Sep;33(9):631-6
references: 10995201
references: FASEB J. 2003 Jul;17(10):1195-214
references: 12832285
references: Chem Rev. 1998 May 7;98(3):1109-1152
references: 11848927
references: Chemphyschem. 2000 Dec 15;1(4):195-8
references: 23696320
references: Crit Rev Biochem Mol Biol. 2005 Mar-Apr;40(2):115-28
references: 15814431
references: Biopolymers. 1979 May;18(5):1149-70
references: 435611
references: Chem Rev. 2006 Feb;106(2):489-505
references: 16464016
references: J Biol Chem. 2000 Aug 25;275(34):26136-43
references: 10851235
references: Free Radic Res Commun. 1990;11(4-5):195-206
references: 1965722
references: J Am Chem Soc. 2003 Aug 27;125(34):10213-8
references: 12926943
references: Mutagenesis. 2005 Nov;20(6):399-410
references: 16199526
references: Acc Chem Res. 2001 Feb;34(2):159-70
references: 11263874
references: Annu Rev Biochem. 2005;74:283-315
references: 15952889
references: Biophys J. 2007 Aug 1;93(3):770-86
references: 17496048
references: J Phys Chem B. 2008 Aug 28;112(34):10752-7
references: 18680360