Structure of a duplex DNA containing a thymine glycol residue in solution.
Oxidative stress, ionizing radiation, and other events can induce the oxidation of the thymine in DNA to thymine glycol. The presence of thymine glycol can have significant biological consequences, and there are specific repair enzymes for thymine glycol in a wide range of organisms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combined use of NMR and restrained molecular dynamics. The duplex of d(C1G2C3G4A5Tg6A7C8G9C10C11) paired with d(G22C21G20C19T18A17T16G15C14G13G12), with Tg indicating thymine glycol, has been used for these studies. The structure shows that the thymine glycol induces a significant, localized structural change with the thymine glycol largely extrahelical. This structural information is consistent with the biological consequences of thymine glycol in DNA. This structure is compared with that of a DNA duplex with an abasic site in the same sequence context.
Kung
H C
HC
Department of Chemistry, Wesleyan University, Middletown, Connecticut 06459, USA.
Bolton
P H
PH
D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013499:Surface Properties; D013941:Thymine / Q000031:analogs & derivatives*
C029389:thymine glycol; D004247:DNA; D013941:Thymine