在中心纯素基的DNA中形成无痕的双重损伤
Liwei Zheng1, Marc M Greenberg1
1Department of Chemistry , Johns Hopkins University , 3400 North Charles Street , Baltimore , Maryland 21218 , United States.
Journal of the American Chemical Society
|May 9, 2018
概括
通过无痕迹的途径引发DNA合损伤. 这种机制涉及2'-脱氧腺-N6-yl基,在玛放射溶解过程中产生显著的DNA损伤.
科学领域:
- DNA 损伤和修复
- 辐射化学
- 核酸基的化学作用
背景情况:
- 以为中心的核酸基是放射解和氧化剂对DNA损伤的关键中间体.
- 它们在病变形成中的精确反应性和作用尚不完全理解.
研究的目的:
- 研究独立生成的2 - 脱氧腺-N6-yl基 (dA•) 的反应性.
- 阐明dA•启动协同DNA损伤的机制.
主要方法:
- 独立生成dA•和T•基.
- 液体染色学 - 双重质谱学 (LC-MS/MS)
- 同位素标记和化学反应实验.
主要成果:
- dA•通过从相邻的胺中抽取气,形成T•,从而启动依赖于O2的双重损伤.
- 该过程产生5 -OxodGuo-fdU并列损伤,特定序列的产量>27%.
- 在抽取过程中,dA•被修复为dA,使其参与无痕迹.
结论:
- 2 - 脱氧腺-N6-yl激素启动了一种新的,无痕迹的 DNA 损伤形成途径.
- 这种机制在γ放射溶解过程中对DNA损伤有显著的作用.
- 这些发现可能广泛适用于核酸中的以为中心的基.
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