一个超模块化的FHA/BRCT重复架构调解Nbs1适配器功能,以应对DNA损伤
Janette Lloyd1, J Ross Chapman, Julie A Clapperton
1Division of Molecular Structure, Medical Research Council National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.
Cell
|October 7, 2009
概括
在DNA修复过程中,Mre11/Rad50/Nbs1 (MRN) 复合体至关重要. 这项研究揭示了Nbs1
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:
- Mre11/Rad50/Nbs1 (MRN) 复合体对于DNA损伤反应通路至关重要.
- 虽然Mre11和Rad50是众所周知的,但Nbs1的确切功能仍然不清楚.
- 了解Nbs1的分子机制是解读DNA修复信号的关键.
研究的目的:
- 阐明Nbs1在DNA修复中的作用的分子基础.
- 描述Nbs1与其他DNA修复蛋白的结构和功能相互作用.
- 调查保存的基在Nbs1介导的信号传输中的作用.
主要方法:
- 进行X射线晶体学以确定裂变酵母Nbs1的N终端区域的结构.
- 生物化学试验分析蛋白质与蛋白质相互作用.
- 在酵母中进行功能性研究,以评估DNA损伤抵抗力.
主要成果:
- 揭示了Nbs1 N-终端区域的一个新的,保存的结构,集成FHA和BRCT域.
- 在Mdc1和Ctp1中的二酸化基因被确定为Nbs1.1的保守结合标.
- Nbs1通过其FHA域与Ctp1的相互作用对于DNA损伤抵抗至关重要.
- 人类Nbs1通过FHA和BRCT领域与Mdc1相互作用.
结论:
- 在Nbs1中,FHA和BRCT域的结构凝聚对于其适应器功能至关重要.
- 保存的基互动调解了Nbs1在DNA损伤反应信号传递中的作用.
- Nbs1充当一个关键的支架,通过与Mdc1和Ctp1的相互作用整合信号通路.
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