双重DNA寡合体中氧化损伤的核基:在胺-胺错配对的反应中
Joshy Joseph1, Gary B Schuster
1School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Journal of the American Chemical Society
|September 15, 2009
概括
在DNA中,氨酸-氨酸不匹配阻断了基因离子运动,成为首选的反应场所. 在错误配对中用乌拉替换胺突出了其作为反应部位和阻碍充电运输的作用.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 摄影化学的使用.
背景情况:
- 已知氨酸-氨酸 (TT) 不配对阻碍了DNA内的长距离基质离子迁移.
- 这些不匹配代表双重DNA寡合体中的高度反应性位点.
研究的目的:
- 调查TT不配对在基离子迁移和DNA寡合体中的反应性中的作用.
- 为了阐明TT不匹配对光诱导氧化后DNA链裂变的影响.
主要方法:
- 一个仅由A/T基对组成的DNA寡合体的合成,具有重复的TT步骤和一个 antraquinone光敏感剂.
- 紫外线照射以诱导单电子氧化和随后对DNA链裂变模式的分析.
- 对TT不匹配的特定场所修改,包括用 uracil 替换,以评估反应性和运输效应.
主要成果:
- DNA寡合物的光氧化导致了基离子的形成,在TT阶段发生了优先反应和链裂变.
- 引入远程GG步骤显著降低了TT步骤中的反应性,裂变主要发生在GG步骤中.
- 寡合体内的TT误对导致了误对部位和前面的TT阶段的链裂变,同时阻断了远程GG阶段的反应.
- 用 uracil 替换错配中的一个胺证实了错配作为一个反应性位点和一个阻碍激素离子跳跃的障碍.
结论:
- 氨酸-氨酸不匹配对DNA中长距离的激素离子迁移起着显著的障碍.
- 这些不配对是激素离子反应和随后的DNA链裂变的首选地点.
- 观察到的效应可能与胺-胺不匹配的摇摆基对结构有关.
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