CHARACTERIZATION OF THE EFFECTS OF A THYMINE GLYCOL RESIDUE ON THE STRUCTURE, DYNAMICS, AND STABILITY OF DUPLEX DNA BY NMR

A duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dih ydrothymidine) has been studied by NMR and other methods. Oxidative st ress, ionizing radiation, and other causes can induce the oxidation of thymine to thymine glycol. The presence of thymine glycol is known to have significant biological consequences, and there are repair enzyme s for thymine glycol in a wide range of organisms. These studies have been carried out on the DNA duplex of d(C1G2C3A4G5Tg6C7A8G9C10C11) pai red with d(G22C21G20T19C18A17G16T15C14G13G12), with Tg indicating thym ine glycol. The presence of thymine glycol lowers the thermal stabilit y of duplex DNA. The NMR results indicate that thymine glycol induces a large, localized structural change in duplex DNA with the thymine gl ycol base being extrahelical as well as the opposing base on the compl ementary strand. This structural information is consistent with the bi ological consequences of thymine glycol in DNA.