One-electron oxidation of DNA: reaction at thymine

Abstract

The feature article is a review of the reaction of thymine in the one-electron oxidation of duplex DNA. Oxidation of DNA causes chemical reactions that result in remote damage (mutation) to a nucleobase. Normally this reaction occurs at guanine, but in oligonucleotides that lack guanines, or when the DNA contains a thymine–thymine mispair, reaction occurs primarily at thymine notwithstanding its high oxidation potential. Selective substitution of uracil for thymine in TT sequences indicates the operation of a tandem reaction mechanism at adjacent thymines. Analysis of the reaction products suggests that proton-coupled electron transfer generates the 5-thymidyl methyl radical, which is trapped by molecular oxygen to give eventually 5-formyl-2′-deoxyuridine and 5-(hydroxymethyl)-2′-deoxyuridine. In a second process, water adds to the 5,6-double bond of the oxidized thymine giving eventually the cis- and trans-diastereomers of 5,6-dihydroxy-5,6-dihydrothymidine.