启动真核转录合DNA修复的结构基础
Jun Xu1, Indrajit Lahiri2, Wei Wang1
1Division of Pharmaceutical Sciences, Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California San Diego, La Jolla, California 92093, USA.
Nature
|November 24, 2017
概括
酵母中的Cockayne综合征组B (CSB) 蛋白,Rad26,对于转录合修复 (TCR) 是至关重要的. 它的结构揭示了它如何与RNA聚合酶II相互作用以促进DNA修复和转录延长.
科学领域:
- 分子生物学
- DNA 修复机制
- 结构生物学
背景情况:
- 转录合修复 (TCR) 可去除阻断RNA聚合酶II (Pol II) 的DNA损伤.
- 在TCR启动过程中,可凯恩综合征组B (CSB) 蛋白 (酵母Rad26) 早期被引入停滞的Pol II.
- 在CSB的突变导致科凯恩综合征, 一种具有前列腺特征的疾病.
研究的目的:
- 阐明真核细胞TCR启动的分子机制.
- 了解CSB/Rad26如何与被捕的Pol II进行互动.
- 解决Pol II-Rad26复合物的结构.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定Saccharomyces cerevisiae Pol II-Rad26复合物的结构.
- 综合物的结构分析.
- 功能测试以评估Rad26的作用.
主要成果:
- 解决了Pol II-Rad26复合物的冷EM结构.
- Rad26与Pol II的上游DNA结合, 改变了它的路径.
- Rad26的Swi2 / Snf2家族ATPase域促进了Pol II的运动.
结论:
- 在TCR启动和转录延长中,Rad26起着关键作用.
- 该结构提供了Rad26与停滞的Pol II相互作用的见解.
- 这项研究阐明了真核细胞TCR启动的机制.
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