ATP puts the brake on DNA double-strand break repair A new study shows that ATP switches the Mre11-Rad50-Nbs1 repair factor between signaling and processing of DNA ends
ATP puts the brake on DNA double-strand break repair A new study shows that ATP switches the Mre11-Rad50-Nbs1 repair factor between signaling and processing of DNA ends
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DOI：
10.1002/bies.201400102
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发表时间：
2014-12-01
期刊：
影响因子：
4
通讯作者：
Hopfner, Karl-Peter
中科院分区：
文献类型：
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作者：
Hopfner, Karl-Peter
DNA双链断裂（DSBs）是最有害的DNA损伤形式之一，可导致细胞失活或染色体畸变。Mre11-Rad50-Nbs1 (MRN) atp -核酸酶复合体是细胞对DSB反应的核心参与者，参与DSB的感知和核分解加工，以及通过激活细胞周期检查点激酶ATM参与DSB信号传导。与Rad50结合的ATP将MRN从暴露的Mre11核酸酶位点的开放状态切换到部分隐藏的核酸酶位点的封闭状态。这个开关的功能意义仍然不清楚。一项新的研究表明，ATP与Rad50结合促进DSB的识别、系结和ATM活化，而ATP水解打开核酸酶活性位点，促进DSB的加工。因此，MRN作为功能开关出现，可能协调从信号到dsb处理的时间过渡。
DNA double-strand breaks (DSBs) are one of the most deleterious forms of DNA damage and can result in cell inviability or chromosomal aberrations. The Mre11-Rad50-Nbs1 (MRN) ATPase-nuclease complex is a central player in the cellular response to DSBs and is implicated in the sensing and nucleolytic processing of DSBs, as well as in DSB signaling by activating the cell cycle checkpoint kinase ATM. ATP binding to Rad50 switches MRN from an open state with exposed Mre11 nuclease sites to a closed state with partially buried nuclease sites. The functional meaning of this switch remained unclear. A new study shows that ATP binding to Rad50 promotes DSB recognition, tethering, and ATM activation, while ATP hydrolysis opens the nuclease active sites to promote processing of DSBs. MRN thus emerges as functional switch that may coordinate the temporal transition from signaling to processing of DSBs.