XPF与TOP2B相互作用,用于R循环处理和DNA循环在活跃转录的基因上
Georgia Chatzinikolaou1, Kalliopi Stratigi1, Athanasios Siametis1,2
1Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, GR70013, Heraklion, Crete, Greece.
Science advances
|November 8, 2023
概括
这项研究揭示了RNA-DNA混合体 (R环) 在转录过程中是如何处理的. 核酸切除修复因子XPF,与TOP2B和CTCF/凝聚素一起,促进R循环分辨率,影响DNA循环和基因激活.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 协同转录的RNA-DNA混合体 (R-循环) 通过导致DNA损伤,对基因组完整性构成风险.
- 通过R循环调节基因活性的精确机制在很大程度上是未知的.
研究的目的:
- 阐明转录期间R循环处理的基础分子机制.
- 研究核酸切除修复因子XPF在R循环分辨率和基因调节中的作用.
主要方法:
- 同免疫沉测试以确定蛋白质相互作用.
- 染色体免疫沉 (ChIP) 评估蛋白质对基因促进体的招募.
- 对DNA损伤反应标记物和DNA循环的分析.
主要成果:
- XPF与CTCF和凝聚素子单元 (SMC1A,SMC3) 相互作用,在转录激活过程中调解R循环依赖的DNA循环.
- XPF将TOP2B招募到活跃的基因促进器中,促进双链断裂和DNA损伤反应激活.
- TOP2B 废除损害了 XPF,CTCF 和凝聚素的招募,阻碍了 DNA 循环和 R 循环处理.
结论:
- 在转录激活过程中,XPF,TOP2B和CTCF/凝聚素复合体对于处理R循环至关重要.
- 这一途径对于保持基因组完整性和调节基因表达至关重要.
- 这些发现对理解与转录相关的DNA损伤相关的DNA修复缺陷综合征有意义.
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