ATR Mediates a Checkpoint at the Nuclear Envelope in Response to Mechanical Stress

0436138 - ÚMG 2015 RIV US eng J - Journal Article
Kumar, A. - Mazzanti, M. - Mistrik, M. - Košař, Martin - Beznoussenko, G.V. - Mironov, A. A. - Garrè, M. - Parazolli, D. - Shivashankar, G. V. - Scita, G. - Bártek, Jiří - Foiani, M.
ATR Mediates a Checkpoint at the Nuclear Envelope in Response to Mechanical Stress.
Cell. Roč. 158, č. 3 (2014), s. 633-646. ISSN 0092-8674. E-ISSN 1097-4172
Grant - others:Marie Curie Intra-European(IT) 274093
Institutional support: RVO:68378050
Keywords : ATR * Mechanical Stress * cell cycle
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 32.242, year: 2014

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.
Permanent Link: http://hdl.handle.net/11104/0241974