ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration.

Autor:	Kidiyoor GR; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Li Q; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Bastianello G; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Bruhn C; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Giovannetti I; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Mohamood A; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Beznoussenko GV; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Mironov A; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Raab M; Institut Curie/CNRS, Paris, France., Piel M; Institut Curie/CNRS, Paris, France., Restuccia U; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Matafora V; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Bachi A; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Barozzi S; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Parazzoli D; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Frittoli E; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Palamidessi A; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Panciera T; University of Padova, Padova, Italy., Piccolo S; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy.; University of Padova, Padova, Italy., Scita G; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy.; University of Milan, Milan, Italy., Maiuri P; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Havas KM; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy., Zhou ZW; Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany.; School of Medicine, Sun Yat-Sen University, Shenzhen, China., Kumar A; Genome and Cell Integrity Lab, CSIR-Indian Institute of Toxicology Research, Lucknow, India., Bartek J; Danish Cancer Society Research Center, Copenhagen, Denmark.; Karolinska Institute, Stockholm, Sweden., Wang ZQ; Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany.; Friedrich-Schiller University, Jena, Germany., Foiani M; IFOM- FIRC Institute of Molecular Oncology, Milan, Italy. marco.foiani@ifom.eu.; University of Milan, Milan, Italy. marco.foiani@ifom.eu.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2020 Sep 24; Vol. 11 (1), pp. 4828. Date of Electronic Publication: 2020 Sep 24.
DOI:	10.1038/s41467-020-18580-9
Abstrakt:	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.
Databáze:	MEDLINE
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