在双重DNA中的cis-5R,6S-和trans-5R,6R-thymine glycol病变的相互转换
Kyle L Brown1, Travis Adams, Vijay P Jasti
1Department of Chemistry, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37235, USA.
Journal of the American Chemical Society
|August 7, 2008
概括
乙氨基甘醇 (Tg) 损伤的DNA改变了DNA双重稳定性和epimer平衡. 互补基的身份影响Tg表层的cis-trans比率,影响DNA修复途径.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- DNA损伤和修复的过程
背景情况:
- 乙胺糖醇 (Tg) 是由活性氧物种氧化乙胺的产物,是一种常见的DNA损伤.
- Tg表皮质 (cis和trans) 的立体化学可以影响DNA修复机制.
- 了解Tg对DNA结构和稳定性的影响,对于理解其生物学后果至关重要.
研究的目的:
- 为了研究将胺糖醇 (Tg) 纳入DNA复合体的结构和热力学后果.
- 确定互补基的身份 (腺因或关氨酸) 如何影响Tg表皮化和DNA双重稳定性.
- 探索Tg平衡和DNA修复之间的关系.
主要方法:
- 在5R Tg损伤的特定地点内,将其纳入一个寡度氧核酸.
- 修改过的寡度氧核酸与含有腺素 (A) 或关氨酸 (G) 的补充链进行化.
- 核磁共振 (NMR) 光谱法用于确定epimer比率.
- 热变性化研究 (T(m)) 来评估DNA双重稳定性.
- 双重化的热力学分析 (自由能量,度).
主要成果:
- Tg损伤破坏了DNA复杂体中的键,而不考虑补充基.
- cis-5R,6S:trans-5R,6R Tg 经体的平衡比受到补充基的影响:Tg x A 的 7:3 和 Tg x G 的 cis.
- 与未经修改的双重复合相比,含有Tg的DNA双重复合显示出化温度 (T(m)) 降低了13°C.
- 两种Tg x A和Tg x G的配对都使化的自由能量增加了3kcal/mol,Tg x G在度上更受青.
结论:
- 提氨基甘醇的结合使DNA复杂体不稳定,并降低了它们的化温度.
- 互补基调节Tg表层之间的平衡,这表明了调节DNA修复的机制.
- 这些发现提供了关于氧化DNA损伤如何影响DNA结构的见解,并被修复酶识别.
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