在DNA损伤引起的转录应激中,染色质状态和ATM信号之间的交叉声
Irene Salas-Armenteros1, Maarten Klunder1, Wim Vermeulen2
1Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Centre, Rotterdam, 3015 GD, The Netherlands.
The EMBO journal
|August 26, 2025
概括
DNA损伤反应 (DDR) 涉及染色体的变化. 停滞的RNA聚合酶II触发了乙化,R循环形成和ATM信号,显示了染色体和DDR通路之间的交叉调节.
科学领域:
- 分子生物学
- 细胞生物学
- 基因组学
背景情况:
- DNA损伤反应 (DDR) 对于保持基因组稳定性至关重要.
- 染色体结构和DDR信号通路之间存在联系.
- 在转录阻断DNA损伤过程中这种相互作用的机制尚未完全理解.
研究的目的:
- 研究对转录阻断DNA损伤的反应中的染色质修饰和DDR信号之间的相互作用.
- 阐明连接RNA聚合酶II停滞到DDR激活的分子机制.
主要方法:
- 染色体乙化和基因组修饰的分析.
- 研究RNA:DNA杂交 (R-循环) 的形成.
- 评估ATM信号通路的激活和下游激酶活性 (p38MAPK/MSK1).
主要成果:
- 在DNA损伤处停滞的RNA聚合酶II通过p300诱导局部染色体乙化.
- 染色体放松促进结合体解离和R环形成,激活ATM.
- 激活ATM导致H2A.X酸化和p38MAPK/MSK1依赖的H3S10酸化,改变色素构造.
结论:
- 转录阻断的DNA损伤触发了涉及染色体乙化和R循环形成的DDR途径.
- 通过染色质状态调节ATM信号,反过来影响染色质构成.
- 染色体和ATM信号之间的交叉调节是细胞对转录应激反应的关键机制.
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