Journal article
8-Oxoguanine enhances bending of DNA that favors binding to glycosylases
Journal of the American Chemical Society, Vol.125(20), pp.6331-6336
05/21/2003
Handle:
https://hdl.handle.net/2376/109619
PMID: 12785867
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.
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Details
- Title
- 8-Oxoguanine enhances bending of DNA that favors binding to glycosylases
- Creators
- John H Miller - Washington State University Tri-Cities, Richland 99352, USA. jhmiller@tricity.wsu.eduCheng-Chih P Fan-ChiangT P StraatsmaMichael A Kennedy
- Publication Details
- Journal of the American Chemical Society, Vol.125(20), pp.6331-6336
- Academic Unit
- Engineering and Applied Sciences (TRIC), School of
- Publisher
- United States
- Identifiers
- 99900547362101842
- Language
- English
- Resource Type
- Journal article