一个为TRF2-介导的染色体末端保护的两步机制
Keiji Okamoto1, Cristina Bartocci, Iliana Ouzounov
1Laboratory of Chromosome Biology and Genomic Stability, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Nature
|February 8, 2013
概括
端粒蛋白TRF2 (TERF2) 使用两步机制来保护染色体末端. 它首先抑制ATM激活,然后抑制下游DNA损伤信号,防止融合.
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:
- 哺乳动物的端粒,在染色体的末端,受到shelterin复合体的保护.
- 在shelterin中,TRF2 (TERF2) 对于终端保护至关重要,抑制ATM激活并防止染色体端到端融合.
研究的目的:
- 确定TRF2的分子特性,对小鼠细胞中染色体末端的保护至关重要.
- 为了阐明TRF2-介导的端粒末端保护的机制.
主要方法:
- 在小鼠胚胎纤维细胞中研究了TRF2的分子特性.
- 分析了TRF2在抑制ATM激活和下游DNA损伤反应 (DDR) 信号传输中的作用.
- 研究了RNF168,BRCC3和UBR5在TRF2-介导的末端保护中的参与.
主要成果:
- 为了抑制ATM激活,TRF2的二分化域是必要的,这是DDR的初始步骤.
- TRF2独立地通过调节E3泛素酶RNF168.8.抑制下游DDR信号.
- 通过BRCC3和UBR5抑制RNF168足以防止染色体端到端的融合.
结论:
- TRF2采用了为端粒末端保护的两步机制.
- 这种机制解释了DDR蛋白如何在没有启动破坏性修复的情况下存在于端粒.
- TRF2的功能涉及阻断初始ATM激活和下游信号传播的不同步骤.
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