Thymidine glycol: the effect on DNA molecular structure and enzymatic processing

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• 作者：Nina G. Dolinnaya ; Elena A. Kubareva ; Elena A. Romanova ; Roman M. Trikin ; Tatiana S. Oretskaya ; ^{oretskaya@belozersky.msu.ru}
• 关键词：Oxidative DNA damage ; Thymine glycol repair ; Translesion synthesis ; Alteration in DNA structure ; Tandem (clustered) lesions
• 刊名：Biochimie
• 出版年：2013
• 出版时间：February, 2013
• 年：2013
• 卷：95
• 期：2
• 页码：134-147
• 全文大小：865 K

文摘

Thymine glycol (Tg) in DNA is a biologically active oxidative damage caused by ionizing radiation or oxidative stress. Due to chirality of C5 and C6 atoms, Tg exists as a mixture of two pairs of cis and trans diastereomers: 5R cis-trans pair (5R,6S; 5R,6R) and 5S cis-trans pair (5S,6R; 5S,6S). Of all the modified pyrimidine lesions that have been studied to date, only thymine glycol represents a strong block to high-fidelity DNA polymerases in?vitro and is lethal in?vivo. Here we describe the preparation of thymine glycol-containing oligonucleotides and the influence of the oxidized residue on the structure of DNA in different sequence contexts, thymine glycol being paired with either adenine or guanine. The effect of thymine glycol on biochemical processing of DNA, such as biosynthesis, transcription and repair in?vitro and in?vivo, is also reviewed. Special attention is paid to stereochemistry and 5R cis-trans epimerization of Tg, and their relation to the structure of DNA double helix and enzyme-mediated DNA processing. Described here are the comparative structure and properties of other forms of pyrimidine base oxidation, as well as the role of Tg in tandem lesions.