9-1-1 DNA 检查点的结构,从开始到结束的间隙加载,以及生物学上的分支
Fengwei Zheng1, Roxana E Georgescu2, Nina Y Yao2
1Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Cell reports
|July 1, 2023
概括
Rad24-RFC优先加载911检查点在DNA间隙上的DNA末端上. 这表明9-1-1在DNA缺口修复和信号传递中发挥着直接作用.
科学领域:
- 分子生物学分子生物学
- 在DNA复制和修复过程中,
- 细胞信号传输 细胞信号传输
背景情况:
- 众所周知,Rad24-RFC将9-1-1检查点子加载到缩的5'DNA末端上.
- 对于Rad24-RFC加载的精确机制和基质偏好仍然不完全理解.
研究的目的:
- 为了调查Rad24-RFC为加载911-1紧固件的基板偏好.
- 为了阐明Rad24-RFC介导的9-1-1加载到DNA结构上的结构基础.
主要方法:
- 生物化学测定用于捕获Rad24-RFC-9-1-1加载中间体.
- 进行X射线晶体学以确定Rad24-RFC-9-1-1复合体在缺口DNA上的结构.
- 对DNA结合和加载机制的分析.
主要成果:
- Rad24-RFC表明,人们更喜欢将9-1-1紧固件装载到DNA间隙上,而不是入5'端.
- 结构分析显示Rad24-RFC不能融化DNA末端,而Rad24循环限制双重DNA长度.
- 这些发现解释了对差距>5-nt ssDNA 的偏好.
结论:
- Rad24-RFC对DNA缺口的偏好表明911在缺口修复中发挥了作用.
- 9-1-1可以直接与转变损伤合成 (TLS) 聚合酶相互作用.
- 这项工作强调了911在DNA损伤反应中的双重作用:信号和修复.
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