在Rad17-Rad9-Hus1-Rad1-Rhino复合体中,能量相当的结构转换是ATR依赖的DNA损伤反应从激活到维护到停活的连续进展的基础
Yasunori Fukumoto1, Ryuzaburo Yuki2, Yasumitsu Ogra1
1Laboratory of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Nucleic acids research
|February 16, 2026
概括
这项研究揭示了犀牛蛋白如何帮助维持和禁用ATR-DNA损伤反应 (ATR-DDR) 途径. 它显示犀牛聚合复合物,而Rad9 C-终端尾部将它们分解,解释ATR-DDR进展.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 结构生物学 结构生物学
背景情况:
- 人们了解ATR-DDR (ATR-DDR) 的DNA损伤反应的激活,但其维护和非激活机制尚不清楚.
- 犀牛是ATR-DDR通路的一个鲜为人知的组成部分,对其功能至关重要.
研究的目的:
- 阐明控制ATR-DDR通路的维护和失活的分子机制.
- 研究犀牛在ATR-DDR进展和复杂组装/拆卸中的作用.
主要方法:
- 结构建模和具有约束力的自由能量计算,以分析复杂的改造.
- 生物化学和计算分析以研究竞争性结合相互作用.
- 量子化学计算以评估中间复合物的结合自由能量.
主要成果:
- 确定了在ATR-DDR进展过程中涉及Rad17,9-1-1综合体和犀牛的结构改造.
- Rad17和Rhino与9-1-1复合体之间的竞争性结合表明,Rad17-9-1-1的复合体从Rad17-9-1-1过渡到Rhino-9-1-1复合体.
- 犀牛的保存图案使得9-1-1复合体的桥梁能够建立,解释了Rad17和Rad9的焦点.
- Rad9的C端尾与Rhino和Rad17竞争,导致检查点复杂的拆卸和失活.
结论:
- 犀牛通过聚合9-1-1复合体,在ATR-DDR维护中发挥关键作用.
- Rad9 C-终端尾部通过复杂的拆卸提供了一个ATR-DDR失活的机制.
- 在Rad17-9-1-1-犀牛复合体中,能量相当的结构转变解释了ATR-DDR的顺序进展.
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