RNF8通过基因素普遍存在和检查点蛋白质组装来转化DNA损伤信号
Michael S Y Huen1, Robert Grant, Isaac Manke
1Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell
|November 16, 2007
概括
RNF8对于早期的DNA损伤反应至关重要,有助于检查点蛋白质的积累和DNA修复. 缺乏RNF8的细胞显示细胞周期检查点受损,对DNA损伤的敏感性增加.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- DNA损伤反应 (DDR) 涉及翻译后的修改.
- 细胞循环检查点,DNA修复,衰老和亡都由DDR进行调节.
研究的目的:
- 研究RNF8在早期DNA损伤反应中的作用.
- 阐明RNF8在DDR中发挥作用的分子机制.
主要方法:
- 进行X射线晶体学以确定RNF8.8的FHA域的结构.
- 细胞测试以评估RNF8枯竭对DNA损伤反应通路的影响.
- 蛋白质与蛋白质相互作用和无处不在事件的分析.
主要成果:
- RNF8促进了BRCA1和53BP1对受损的染色质的招募.
- 通过其FHA域,RNF8以相依赖的方式与MDC1结合.
- 在DNA损伤部位的RNF8 ubiquitinatesH2AX和其他基质.
- 缺乏RNF8的细胞表现出有缺陷的G2/M检查点和对电离辐射 (IR) 的敏感性增加.
结论:
- RNF8是一种新型的DNA损伤反应蛋白.
- RNF8在DDR中整合了酸化和无处不在的信号.
- RNF8在细胞对基因毒性压力的反应中起着至关重要的作用.
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