ATR signalling: more than meeting at the fork.
ATR signalling: more than meeting at the fork.
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DOI：
10.1042/bj20102162
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发表时间：
2011-06-15
期刊：
影响因子：
--
通讯作者：
Cortez D
中科院分区：
文献类型：
--
作者：
Nam EA;Cortez D
通过DNA损伤反应保存基因组的完整性对于预防疾病至关重要。共济失调毛细血管扩张突变和rad3相关（ATR）是生命所必需的，是DNA损伤反应的主要调节器，特别是在DNA复制过程中。ATR控制和协调DNA复制起始触发、复制叉稳定性、细胞周期检查点和DNA修复。自15年前被发现以来，ATR的激活和信号传导模型已经出现，该模型涉及DNA损伤位点的定位和通过蛋白质-蛋白质相互作用的激活。最近的研究增加了对典型ATR途径的越来越详细的理解，并认识到典型模型并不能完全反映ATR调节的复杂性。在这里，我们回顾了ATR信号传导过程，重点关注从鉴定新的ATR相互作用蛋白和底物中获得的机制发现。我们讨论了如何将这些新见解纳入ATR调控模型，并指出我们对这一重要基因组维持途径的理解存在重大差距。
Preservation of genome integrity via the DNA damage response is critical to prevent disease. Ataxia-telangiectasia mutated and Rad3-related (ATR) is essential for life and functions as a master regulator of the DNA damage response, especially during DNA replication. ATR controls and coordinates DNA replication origin firing, replication fork stability, cell cycle checkpoints, and DNA repair. Since its identification 15 years ago, a model of ATR activation and signaling has emerged that involves localization to sites of DNA damage and activation through protein-protein interactions. Recent research has added an increasingly detailed understanding of the canonical ATR pathway, and an appreciation that the canonical model does not fully capture the complexity of ATR regulation. Here we review the ATR signaling process, focusing on mechanistic findings garnered from the identification of new ATR interacting proteins and substrates. We discuss how to incorporate these new insights into a model of ATR regulation, and point out the significant gaps in our understanding of this essential genome maintenance pathway.