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@ARTICLE{Nava:875202,
author = {Nava, Michele M. and Miroshnikova, Yekaterina A. and Biggs,
Leah C. and Whitefield, Daniel B. and Metge, Franziska and
Boucas, Jorge and Vihinen, Helena and Jokitalo, Eija and Li,
Xinping and García Arcos, Juan Manuel and Hoffmann, Bernd
and Merkel, Rudolf and Niessen, Carien M. and Dahl, Kris
Noel and Wickström, Sara A.},
title = {{H}eterochromatin-{D}riven {N}uclear {S}oftening {P}rotects
the {G}enome against {M}echanical {S}tress-{I}nduced
{D}amage},
journal = {Cell},
volume = {181},
number = {4},
issn = {0092-8674},
address = {New York, NY},
publisher = {Elsevier},
reportid = {FZJ-2020-01870},
pages = {800-817},
year = {2020},
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.},
cin = {IBI-2},
ddc = {610},
cid = {I:(DE-Juel1)IBI-2-20200312},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32302590},
UT = {WOS:000533623900008},
doi = {10.1016/j.cell.2020.03.052},
url = {https://juser.fz-juelich.de/record/875202},
}