TY  - JOUR
AU  - Nava, Michele M.
AU  - Miroshnikova, Yekaterina A.
AU  - Biggs, Leah C.
AU  - Whitefield, Daniel B.
AU  - Metge, Franziska
AU  - Boucas, Jorge
AU  - Vihinen, Helena
AU  - Jokitalo, Eija
AU  - Li, Xinping
AU  - García Arcos, Juan Manuel
AU  - Hoffmann, Bernd
AU  - Merkel, Rudolf
AU  - Niessen, Carien M.
AU  - Dahl, Kris Noel
AU  - Wickström, Sara A.
TI  - Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage
JO  - Cell
VL  - 181
IS  - 4
SN  - 0092-8674
CY  - New York, NY
PB  - Elsevier
M1  - FZJ-2020-01870
SP  - 800-817
PY  - 2020
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:32302590
UR  - <Go to ISI:>//WOS:000533623900008
DO  - DOI:10.1016/j.cell.2020.03.052
UR  - https://juser.fz-juelich.de/record/875202
ER  -