端粒
DNA糖基化酶
生物
DNA损伤
DNA
DNA修复
氧化应激
衰老
鸟嘌呤
基底切除修复术
端粒结合蛋白
细胞生物学
遗传学
生物化学
分子生物学
DNA结合蛋白
基因
核苷酸
转录因子
作者
David B. Rhee,Avik Ghosh,Jian Lü,Vilhelm A. Bohr,Yie Liu
出处
期刊:DNA Repair
[Elsevier]
日期:2011-01-02
卷期号:10 (1): 34-44
被引量:108
标识
DOI:10.1016/j.dnarep.2010.09.008
摘要
Telomeres are nucleoprotein complexes at the ends of linear chromosomes in eukaryotes, and are essential in preventing chromosome termini from being recognized as broken DNA ends. Telomere shortening has been linked to cellular senescence and human aging, with oxidative stress as a major contributing factor. 7,8-Dihydro-8-oxogaunine (8-oxodG) is one of the most abundant oxidative guanine lesions, and 8-oxoguanine DNA glycosylase (OGG1) is involved in its removal. In this study, we examined if telomeric DNA is particularly susceptible to oxidative base damage and if telomere-specific factors affect the incision of oxidized guanines by OGG1. We demonstrated that telomeric TTAGGG repeats were more prone to oxidative base damage and repaired less efficiently than non-telomeric TG repeats in vivo. We also showed that the 8-oxodG-incision activity of OGG1 is similar in telomeric and non-telomeric double-stranded substrates. In addition, telomere repeat binding factors TRF1 and TRF2 do not impair OGG1 incision activity. Yet, 8-oxodG in some telomere structures (e.g., fork-opening, 3′-overhang, and D-loop) were less effectively excised by OGG1, depending upon its position in these substrates. Collectively, our data indicate that the sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing.
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