单链DNA与转录因子PafBC结合,触发了菌根细菌的DNA损伤反应
Charlotte M Schilling1, Rafal Zdanowicz1, Julius Rabl2
1ETH Zurich, Institute of Molecular Biology and Biophysics, 8093 Zurich, Switzerland.
Science advances
|February 7, 2025
概括
单链DNA与PafBC转录因子的WYL域结合,激活了其在真菌细菌中的DNA损伤反应. 这种结合是动态的,DNA修复导致PafBC失活.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 菌根菌中的DNA损伤反应是由PafBC转录因子调节的.
- PafBC是一种含有WYL域的蛋白质,通过西格玛适应激活基因转录.
- 检测DNA损伤和激活PafBC的机制仍然难以捉摸.
研究的目的:
- 通过PafBC阐明DNA损伤传感的机制.
- 为了确定DNA损伤信号如何转化为PafBC激活.
- 描述PafBC-ssDNA相互作用的结构和动态方面.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定PafBC-DNA复合物的结构.
- 生物化学实验分析PafBC-ssDNA结合动态.
主要成果:
- 与PafBC WYL域结合的单链DNA (ssDNA) 激活了转录因子.
- 化EM揭示了活跃的PafBC复合体中的新型ssDNA-WYL域相互作用模式.
- 生物化学分析表明,在DNA修复后,有动态的ssDNA结合和PafBC失活.
结论:
- ssDNA结合是响应DNA损伤时PafBC激活的关键机制.
- 由于ssDNA结合的动态性,可以调节PafBC活动.
- 这些发现扩大了对WYL域蛋白在DNA损伤反应中的作用的理解.
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