UBE2D3通过RNF168的多层次控制来协调ATM信号来促进NHEJ
Zeliha Yalçin1, Shiu Yeung Lam1, Marieke H Peuscher1
1Division of Oncogenomics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, the Netherlands.
Nature communications
|June 12, 2024
概括
无素结合酶UBE2D3调节DNA损伤反应 (DDR) 并促进非同类末端结合 (NHEJ) 在端粒. 它协调ATM和RNF168活动,确保基因组完整性.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 基因组完整性至关重要,它依赖于受控的DNA损伤反应 (DDR) 和修复途径.
- 酸化和无处不在是DDR中关键的翻译后修改,但它们的协调尚未完全理解.
研究的目的:
- 为了确定ATM激酶诱导的DDR的调节者,促进端粒非同质末端结合 (NHEJ).
- 阐明 UBE2D3 在协调 DDR 信号和 NHEJ 的作用.
主要方法:
- 研究了在DNA损伤反应中泛素结合酶UBE2D3的功能.
- 使用的技术来评估染色质泛化,蛋白质招募 (53BP1) 和酶活性 (ATM,KAP1酸化).
- 分析了UBE2D3缺乏对端粒NHEJ和调节通路的影响.
主要成果:
- UBE2D3调节了ATM诱导的DDR,并促进了端粒NHEJ.
- UBE2D3通过RNF168.8促进了染色质的无处不在和53BP1的招募.
- UBE2D3限制了RNF168的积累,并促进了KAP1-S824的酸化,抵消了异常的酸酶活性.
结论:
- UBE2D3是NHEJ的多层监管者,协调ATM和RNF168活动.
- DDR中的负调节电路,涉及RNF168和限制KAP1酸化的酸酶,受到UBE2D3.3的约束.
- 通过精确控制DNA修复途径,UBE2D3在维持基因组完整性方面发挥着至关重要的作用.
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