基因组H1对在DNA损伤后启动和放大泛素信号
Tina Thorslund1, Anita Ripplinger1, Saskia Hoffmann1
1Ubiquitin Signaling Group, Protein Signaling Program, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen, Denmark.
Nature
|October 28, 2015
概括
基因组H1是RNF8-UBC13在DNA双链断裂信号中的关键标. 这一发现解释了RNF8和UBC13如何招募RNF168来修复部位,保持基因组稳定性.
科学领域:
- 分子生物学
- 遗传学
- 生物化学
背景情况:
- DNA双链断裂 (DSB) 是一种关键的DNA损伤.
- 在DSB附近的染色质的无处不在会招募DNA修复因子.
- 在DSB反应中,RNF8,RNF168和UBC13是关键的E3/E2泛素连接酶.
研究的目的:
- 阐明RNF8和UBC13在招募RNF168和下游因素到DSB的作用.
- 在DSB信号中识别RNF8和K63连接无处不在的关键基质.
主要方法:
- 研究了人类细胞中DSB位点的无处不在事件.
- 使用生物化学测试来确定蛋白质与ubiquitin的相互作用.
- 评估了基因组H1表达对DNA修复因子的影响.
主要成果:
- 在DSB位点中,RNF8和UBC13调解K63连接的无处不在,主要准基因组H1,而不是核心基因组.
- RNF168 UDM1 模块识别了K63无处不在的素H1,解释了RNF168对DSB的招募.
- 降低的希斯H1水平会损害在DSB部位的基合物和修复因子的积累.
结论:
- 基因组H1是RNF8-UBC13在DSB信号传递中的主要点.
- 基因组稳定因子的识别标记是基因组H1的翻译后修改.
- 这扩展了基因组代码概念,包括DNA修复途径中的链接基因组修饰.
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