Nava, Michele M., Miroshnikova, Yekaterina A., Biggs, Leah C., Whitefield, Daniel B., Metge, Franziska, Boucas, Jorge, Vihinen, Helena ORCID: 0000-0003-3862-9237, Jokitalo, Eija ORCID: 0000-0002-4159-6934, Li, Xinping, Arcos, Juan Manuel Garcia, Hoffmann, Bernd, Merkel, Rudolf ORCID: 0000-0003-3178-3282, Niessen, Carien M., Dahl, Kris Noel and Wickstrom, Sara A. (2020). Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage. Cell, 181 (4). S. 800 - 840. CAMBRIDGE: CELL PRESS. ISSN 1097-4172

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Abstract

Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a calcium-dependent nuclear softening driven by loss of H3K9me3-marked heterochromatin. The resulting changes in chromatin rheology and architecture are required to insulate genetic material from mechanical force. Failure to mount this nuclear mechanoresponse results in DNA damage. Persistent, high amplitude stretch induces supracellular alignment of tissue to redistribute mechanical energy before it reaches the nucleus. This tissue-scale mechanoadaptation functions through a separate pathway mediated by cell-cell contacts and allows cells/tissues to switch off nuclear mechanotransduction to restore initial chromatin state. Our work identifies an unconventional role of chromatin in altering its own mechanical state to maintain genome integrity in response to deformation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Nava, Michele M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miroshnikova, Yekaterina A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biggs, Leah C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whitefield, Daniel B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metge, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boucas, JorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vihinen, HelenaUNSPECIFIEDorcid.org/0000-0003-3862-9237UNSPECIFIED
Jokitalo, EijaUNSPECIFIEDorcid.org/0000-0002-4159-6934UNSPECIFIED
Li, XinpingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arcos, Juan Manuel GarciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Merkel, RudolfUNSPECIFIEDorcid.org/0000-0003-3178-3282UNSPECIFIED
Niessen, Carien M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dahl, Kris NoelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wickstrom, Sara A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-333791
DOI: 10.1016/j.cell.2020.03.052
Journal or Publication Title: Cell
Volume: 181
Number: 4
Page Range: S. 800 - 840
Date: 2020
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1097-4172
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA-DAMAGE; CHROMATIN; ARCHITECTURE; ALIGNMENT; STRAIN; ORIENTATION; MORPHOLOGY; PLASTICITY; RECEPTOR; ELEMENTSMultiple languages
Biochemistry & Molecular Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33379

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