与Rad50的Rif2相互作用通过释放Tel1从MRX结合中释放Tel1来对抗检查点信号和DNA结合中的Tel1功能
Paolo Pizzul1, Erika Casari1, Carlo Rinaldi1
1Dipartimento di Biotecnologie e Bioscienze, Università degli Studi di Milano - Bicocca, 20126 Milano, Italy.
Nucleic acids research
|January 5, 2024
概括
酵母Rif2蛋白通过结合Rad50.5来抑制DNA双链断裂 (DSB) 的Tel1激酶激活. 一个rif2-S6E突变增强了这种抑制,损害了DSB终端连接.
科学领域:
- 分子生物学分子生物学
- 修复DNA修复DNA的修复
- 细胞循环规则 细胞循环规则
背景情况:
- 酵母Rif2蛋白通过其MIN动机抑制Mre11核酶和Tel1酶激活.
- Rif2结合Rad50并刺激其ATPase活性,但在DNA双链断裂 (DSB) 中Tel1抑制的确切机制尚不清楚.
研究的目的:
- 为了阐明Rif2-介导的Tel1抑制在DSB的机制.
- 描述Rif2在调节Tel1招聘和活动中的作用.
主要方法:
- 通过AlphaFold-Multimer模型识别Rif2 MIN-Rad50的交互表面.
- 改造了rif2-S6E突变,以增强Rif2-Rad50的相互作用.
- 分析了发针切割,Tel1激活和MRX复杂动态.
主要成果:
- rif2-S6E突变增强了Rif2-Rad50的相互作用,损害了发针切割,并减少了Tel1的激活.
- 通过促进与ADP结合的MRX构成,Rif2直接抑制了Tel1对DSB的招募.
- 对Rad50的Rif2结合减少了Tel1-MRX的相互作用,并损害了DSB的终端连接.
结论:
- Rif2作为Tel1招募到DSB的直接抑制剂.
- Tel1 在 DSB 端的桥接中起着至关重要的作用,这一功能由 Rif2 调节.
- 这项研究揭示了一种控制DNA修复中的Tel1活动的新机制.
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