PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin
PIKK-dependent phosphorylation of Mre11 induces MRN complex inactivation by disassembly from chromatin
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DOI：
10.1016/j.dnarep.2009.07.006
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发表时间：
2009-11-02
期刊：
影响因子：
3.8
通讯作者：
Gautier, Jean
中科院分区：
文献类型：
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作者：
Di Virgilio, Michela;Ying, Carol Y.;Gautier, Jean
Mre11的磷酸化在细胞对DNA双链断裂(DSB)的反应中的作用尚不清楚。在这里，我们证明了PIKKs(PI3Kinase-Related Kinase)通过降低Mre11与DNA的亲和力而导致Mre11在SQ/TQ基序上的磷酸化导致MRN(Mre11-Rad50-Nbs1)复合体与染色质解离。然而，DSB诱导的ATM(共济失调-毛细血管扩张突变)激活并不需要这些残基上Mre11的磷酸化，而取消Mre11去磷酸化会损害ATM信号。我们的研究提供了DNA损伤诱导的Mre11磷酸化的功能特征，并表明MRN失活参与了DSB修复后检查点恢复过程中损伤信号的下调。(C)2009爱思唯尔B.V.保留所有权利。
The role of Mre11 phosphorylation in the cellular response to DNA double-strand breaks (DSBs) is not well understood. Here, we show that phosphorylation of Mre11 at SQ/TQ motifs by PIKKs (PI3 Kinase-related Kinases) induces MRN (Mre11-Rad50-Nbs1) complex dissociation from chromatin by reducing Mre11 affinity for DNA. Whereas phosphorylation of Mre11 at these residues is not required for DSB-induced ATM (Ataxia-Telangiectasia mutated) activation, abrogation of Mre11 dephosphorylation impairs ATM signaling. Our study provides a functional characterization of the DNA damage-induced Mre11 phosphorylation, and suggests that MRN inactivation participates in the down-regulation of damage signaling during checkpoint recovery following DSB repair. (C) 2009 Elsevier B.V. All rights reserved.