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-dihydrothymidine) has been studied by NMR and other methods. Oxidative stress, 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 enzymes for thymine glycol in a wide range of organisms. These studies have been carried out on the DNA duplex of d(C1G2C3A4G5Tg6C7A8G9C10C11) paired with d(G22C21G20T19C18A17G16T15C14G13G12), with Tg indicating thymine glycol. The presence of thymine glycol lowers the thermal stability of duplex DNA. The NMR results indicate that thymine glycol induces a large, localized structural change in duplex DNA with the thymine glycol base being extrahelical as well as the opposing base on the complementary strand. This structural information is consistent with the biological consequences of thymine glycol in DNA.