ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 09 2020
24 09 2020
Historique:
received:
06
06
2019
accepted:
25
08
2020
entrez:
25
9
2020
pubmed:
26
9
2020
medline:
21
10
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32973141
doi: 10.1038/s41467-020-18580-9
pii: 10.1038/s41467-020-18580-9
pmc: PMC7518249
doi:
Substances chimiques
Chromatin
0
ATR protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4828Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : DBT-Wellcome Trust India Alliance
ID : IA/I/16/2/502721
Pays : India
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