活哺乳动物细胞中金-DNA交叉链路的转录抑制
Wee Han Ang1, MyatNoeZin Myint, Stephen J Lippard
1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Journal of the American Chemical Society
|May 7, 2010
概括
来自抗癌药物的-DNA交叉链接阻断了哺乳动物细胞中的转录. 核酸切除修复会去除这些-DNA附加物,恢复转录,这对于理解药物机制至关重要.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 基于的药物是重要的抗癌剂.
- 它们的有效性依赖于DNA交叉链接和转录抑制.
- 在体内了解-DNA附加物处理是至关重要的.
研究的目的:
- 为了研究活哺乳动物细胞中特定站点-DNA交叉链接的处理.
- 阐明核酸切除修复在缓解诱导的转录封锁中的作用.
主要方法:
- 开发了一种活细胞测定方法,使用具有定义-DNA病变的酶记者等离子体.
- 引入全球或特定地点的化等离子体进入哺乳动物细胞.
- 使用的细胞具有合格或缺陷的核酸切除修复 (NER) 系统.
主要成果:
- -DNA交叉链阻碍RNA聚合酶的进展,抑制转录.
- 核酸切除修复 (NER) 有效地去除了-DNA附加物.
- 与NER缺陷细胞不同的是,NER-熟练的细胞在金DNA损伤后恢复了转录.
结论:
- -DNA交叉链接在活细胞中通过核酸切除修复 (NER) 进行处理.
- 对于恢复基抗癌药物中断的转录,NER是必不可少的.
- 这项研究提供了关于药物作用和耐药性的体内机理性见解.
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