How cells activate ATR
How cells activate ATR
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DOI：
10.4161/cc.5.12.2834
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发表时间：
2006-06-15
期刊：
影响因子：
4.3
通讯作者：
Dunphy, William G.
中科院分区：
文献类型：
--
作者：
Kumagai, Akiko;Dunphy, William G.
ATR是对不完全复制和受损DNA的检查点反应的关键上游调节器。然而，目前还不清楚ATR的激酶活性是如何在检查点反应中开启的。TopBP1及其同源物在DNA复制和检查点控制中都是必需的。该实验室最近的一份报告表明，TopBP1作为ATR的激活剂起作用。已知TopBP1在复制应激和DNA损伤部位积累。因此，ATR与停滞复制叉和DNA损伤位点的关键蛋白相互作用触发其激活。这一发现有助于解释基因组中异常的DNA结构如何诱导atr依赖的信号传导过程。
ATR is a critical upstream regulator of checkpoint responses to incompletely replicated and damaged DNA. However, it had not been understood how the kinase activity of ATR is switched on during checkpoint responses. TopBP1 and its homologs are necessary for both DNA replication and checkpoint control. A recent report from this laboratory demonstrated that TopBP1 functions as an activator of ATR. It had been known that TopBP1 accumulates at sites of replicative stress and DNA damage. Thus, interaction of ATR with a critical protein at stalled replication forks and sites of DNA damage triggers its activation. This finding helps to explain how aberrant DNA structures in the genome induce ATR-dependent signaling processes.