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cells, atr, nuclear, cell, pubmed, fig, article, google, scholar, cas, analysis, mechanical, supplementary, migration, atrdefective, chromatin, membrane, nucleus, shatr, control, performed, min, data, central, stress, experiments, yap, nuclei, images, nesprin, nature, dna, buffer, defects, protein, atrdepleted, depletion, envelope, foci, number, membranes, found, size, mice, compression, samples, invaginations, calculated, fret, ruptures,

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nature portfolio cogentech sequencing services privacy policy policies anti-gfp mab-magnetic beads advertising ptrip-cmv-gfp-flag-cgas peptide libraries wild-type gfp-atr rescued embedded poly-di-methyl-siloxane nature 522 nature 15 μm-long micro-fabricated constrictions28 reprints international cancer research swedish research council sun yat-sen university analyzed h2b-mcherry-expressing shatr zhong-wei zhou japan author information authors cells expressing h2b-gfp peer reviewer reports inhibits intra-golgi transport flag-atr-kd plasmid56 primary load-bearing element c9100-50 electron-multiplying ccd cancer research related tools atr-depleted u2os cells clamping tools mcherry-tagged histone h2b atr-depleted hela cells atr-defective cells exhibited dna damage-induced phosphorylation supplementary movie d5-tg istd mix d5-dg istd mix hutchinson-gilford progeria syndrome nuclear circularity index chromatin-nuclear envelope tethers standard phenol–chloroform technique micro-fabricated migration assays atr-defective nuclei collapse linear step-wise increment independent research toxicology research atr/atm phosphorylation target4 heavy-labeled l-lysine long-term adaptive responses

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         headline:ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
         description:ATR responds to mechanical stress at the nuclear envelope and mediates envelope-associated repair of aberrant topological DNA states. By combining microscopy, electron microscopic analysis, biophysical and in vivo models, we report that ATR-defective cells exhibit altered nuclear plasticity and YAP delocalization. When subjected to mechanical stress or undergoing interstitial migration, ATR-defective nuclei collapse accumulating nuclear envelope ruptures and perinuclear cGAS, which indicate loss of nuclear envelope integrity, and aberrant perinuclear chromatin status. ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells. Our findings indicate that ATR ensures mechanical coupling of the cytoskeleton to the nuclear envelope and accompanying regulation of envelope-chromosome association. Thus the repertoire of ATR-regulated biological processes extends well beyond its canonical role in triggering biochemical implementation of the DNA damage response. The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.
         datePublished:2020-09-24T00:00:00Z
         dateModified:2020-09-24T00:00:00Z
         pageStart:1
         pageEnd:16
         license:http://creativecommons.org/licenses/by/4.0/
         sameAs:https://doi.org/10.1038/s41467-020-18580-9
         keywords:
            Cell invasion
            Checkpoint signalling
            Nuclear envelope
            Science
            Humanities and Social Sciences
            multidisciplinary
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      headline:ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
      description:ATR responds to mechanical stress at the nuclear envelope and mediates envelope-associated repair of aberrant topological DNA states. By combining microscopy, electron microscopic analysis, biophysical and in vivo models, we report that ATR-defective cells exhibit altered nuclear plasticity and YAP delocalization. When subjected to mechanical stress or undergoing interstitial migration, ATR-defective nuclei collapse accumulating nuclear envelope ruptures and perinuclear cGAS, which indicate loss of nuclear envelope integrity, and aberrant perinuclear chromatin status. ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells. Our findings indicate that ATR ensures mechanical coupling of the cytoskeleton to the nuclear envelope and accompanying regulation of envelope-chromosome association. Thus the repertoire of ATR-regulated biological processes extends well beyond its canonical role in triggering biochemical implementation of the DNA damage response. The nucleus is a mechanically stiff organelle of the cell and the DNA damage response protein ATR can localize to the nuclear envelope upon mechanical stress. Here, the authors show that ATR may contribute to the integrity of the nuclear envelope and may play a role in cell migration.
      datePublished:2020-09-24T00:00:00Z
      dateModified:2020-09-24T00:00:00Z
      pageStart:1
      pageEnd:16
      license:http://creativecommons.org/licenses/by/4.0/
      sameAs:https://doi.org/10.1038/s41467-020-18580-9
      keywords:
         Cell invasion
         Checkpoint signalling
         Nuclear envelope
         Science
         Humanities and Social Sciences
         multidisciplinary
      image:
         https://media.springernature.com/lw1200/springer-static/image/art%3A10.1038%2Fs41467-020-18580-9/MediaObjects/41467_2020_18580_Fig1_HTML.png
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