title: 8-Oxoguanine enhances bending of DNA that favors binding to glycosylases.
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.
authors.affiliation: Washington State University Tri-Cities, Richland 99352, USA. jhmiller@tricity.wsu.edu
authors.forename: John H
authors.initials: JH
authors.lastname: Miller
authors.forename: Cheng-Chih P
authors.initials: CC
authors.lastname: Fan-Chiang
authors.forename: T P
authors.initials: TP
authors.lastname: Straatsma
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kennedy
mesh_terms: D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D045647:DNA Glycosylases; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000737:chemistry* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases