ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress.
ATR mediates a checkpoint at the nuclear envelope in response to mechanical stress.
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DOI：
10.1016/j.cell.2014.05.046
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发表时间：
2014-07-31
期刊：
影响因子：
64.5
通讯作者：
Foiani M
中科院分区：
文献类型：
--
作者：
Kumar A;Mazzanti M;Mistrik M;Kosar M;Beznoussenko GV;Mironov AA;Garrè M;Parazzoli D;Shivashankar GV;Scita G;Bartek J;Foiani M
ATR控制染色体完整性和染色质动力学。我们之前已经证明酵母Mec1/ATR促进染色质脱离核膜，以抵消DNA复制过程中异常的拓扑转变。在这里，我们提供的证据表明，ATR活动在核膜响应机械应力。人类ATR在S期和前期与核膜相关，渗透应力和机械拉伸在整个细胞周期中将ATR重新定位到核膜上。atr介导的机械反应发生在生理力的范围内，是可逆的，并且独立于DNA损伤信号。atr缺陷细胞表现出异常的染色质凝聚和核膜破裂。我们认为，来自染色体动力学的机械力和核膜上的扭转应力激活ATR来调节核膜的可塑性和染色质与核膜的结合，从而使细胞能够应对这些分子过程所施加的机械应变。ATR定位于S期的核包膜，前期ATR通过向核包膜重新定位来响应机械应力。ATR的机械响应是快速可逆的，ATR协调染色质凝聚和核包膜破裂ATR通过向核包膜重新定位并发出信号来响应各种机械应力，不依赖于dna损伤反应途径。ATR可以使细胞应对分子过程施加的机械应变，如染色体动力学。
ATR controls chromosome integrity and chromatin dynamics. We have previously shown that yeast Mec1/ATR promotes chromatin detachment from the nuclear envelope to counteract aberrant topological transitions during DNA replication. Here, we provide evidence that ATR activity at the nuclear envelope responds to mechanical stress. Human ATR associates with the nuclear envelope during S phase and prophase, and both osmotic stress and mechanical stretching relocalize ATR to nuclear membranes throughout the cell cycle. The ATR-mediated mechanical response occurs within the range of physiological forces, is reversible, and is independent of DNA damage signaling. ATR-defective cells exhibit aberrant chromatin condensation and nuclear envelope breakdown. We propose that mechanical forces derived from chromosome dynamics and torsional stress on nuclear membranes activate ATR to modulate nuclear envelope plasticity and chromatin association to the nuclear envelope, thus enabling cells to cope with the mechanical strain imposed by these molecular processes. ATR localizes at the nuclear envelope in S phase and prophase ATR responds to mechanical stress by relocalizing to the nuclear envelope The ATR mechanical response is fast and reversible ATR coordinates chromatin condensation and nuclear envelope breakdown ATR responds to various kinds of mechanical stress by relocating to the nuclear envelope and signaling, independent of the DNA-damage response pathway. ATR may enable cells to cope with mechanical strain imposed by molecular processes, such as chromosome dynamics.
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影响因子：
64.5
作者：
Casper, AM;Nghiem, P;Glover, TW
通讯作者：
Glover, TW
影响因子：
12.3
作者：
Blasius M;Forment JV;Thakkar N;Wagner SA;Choudhary C;Jackson SP
通讯作者：
Jackson SP
影响因子：
64.5
作者：
Bermejo R;Capra T;Jossen R;Colosio A;Frattini C;Carotenuto W;Cocito A;Doksani Y;Klein H;Gómez-González B;Aguilera A;Katou Y;Shirahige K;Foiani M
通讯作者：
Foiani M
影响因子：
4.5
作者：
Hashash N;Johnson AL;Cha RS
通讯作者：
Cha RS
DOI：
10.1083/jcb.200605080
发表时间：
2006-12-04
期刊：
The Journal of cell biology
影响因子：
--
作者：
Enserink JM;Smolka MB;Zhou H;Kolodner RD
通讯作者：
Kolodner RD