[Show abstract][Hide abstract] ABSTRACT: Molecular dynamics (MD) simulations were carried out on the DNA oligonucleotide GGGAACAACTAG:CTAGTTGTTCCC in its native form and with guanine in the central G(19):C(6) base pair replaced by 8-oxoguanine (8oxoG). A box of explicit water molecules was used for solvation, and Na(+) counterions were added to neutralize the system. The direction and magnitude of global bending were assessed by a technique used previously to analyze simulations of DNA containing a thymine dimer. The presence of 8oxoG did not greatly affect the magnitude of DNA bending; however, bending into the major groove was significantly more probable when 8oxoG replaced G(19). Crystal structures of glycosylases bound to damaged-DNA substrates consistently show a sharp bend into the major groove at the damage site. We conclude that changes in bending dynamics that assist the formation of this kink are a part of the mechanism by which glycosylases of the base excision repair pathway recognize the presence of 8oxoG in DNA.
Journal of the American Chemical Society 06/2003; 125(20):6331-6. · 10.68 Impact Factor