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 thy mine glycol can have significant biological consequences, and there ar e specific repair enzymes for thymine glycol in a wide range of organi sms. The structure of a duplex DNA containing a single thymine glycol (5,6-dihydroxy-5,6-dihydrothymidine) has been determined by the combin ed use of NMR and restrained molecular dynamics. The duplex of d(C(1)G (2)C(3)G(4)A(5)Tg(6)A(7)C(8)G(9)C(10)C(11)) paired with 21)G(20)C(19)T (18)A(17)T(16)G(15)C(14)G(13)G(12)), with Tg indicating thymine glycol , has been used for these studies. The structure shows that the thymin e glycol induces a significant, localized structural change with the t hymine glycol largely extrahelical. This structural information is con sistent with the biological consequences of thymine glycol in DNA. Thi s structure is compared with that of a DNA duplex with an abasic site in the same sequence context.