在DNA中 (5'S) -8,5'-cyclo-2'-deoxyguanosine的结构
Hai Huang1, Rajat S Das, Ashis K Basu
1Department of Chemistry, Center in Molecular Toxicology, Center for Structural Biology, and the Vanderbilt-Ingram Cancer Center, Vanderbilt University , Nashville, Tennessee 37235, USA.
Journal of the American Chemical Society
|November 23, 2011
概括
8,5'-cyclopurine 2'-deoxynucleosides 是来自电离辐射的DNA损伤病变. 这些病变阻断复制,具有变异性,可能导致神经退行,并通过核酸切割修复得到识别.
科学领域:
- 分子生物学分子生物学
- DNA 修复机制的修复机制
- 结构生物学 结构生物学
背景情况:
- 异构体8,5'-cyclopurine 2'-deoxynucleosides是通过电离辐射形成的DNA病变.
- 8,5'-cyclo-2'-deoxyguanosine (cdG) 损伤是大肠杆菌中强有力的复制阻断剂和变异原体.
- 这些病变与xeroderma pigmentosum的神经退行有关,并通过核酸切除修复 (NER) 进行修复.
研究的目的:
- 阐明DNA复合体内S-cdG损伤的结构和热力学后果.
- 了解S-cdG损伤如何影响DNA结构及其被修复酶识别.
主要方法:
- 用NMR衍生的约束装置进行分子动力学模拟.
- 进行紫外线化实验,以评估双重稳定性.
主要成果:
- 在S-cdG损伤诱导了O4'-exo (西) 伪旋转在脱氧糖.
- 核酸扭转角度 (β, γ, χ) 和螺旋参数 (扭转,堆叠) 中观察到显著的干扰.
- 双重不稳定与损伤部位和相邻的基对的结构性扰动相关.
结论:
- 由S-cdG损伤引起的结构扭曲可能是其基因毒性和NER.认可的基础.
- 了解这些结构效应对于理解DNA损伤反应途径至关重要.
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