2021
DOI: 10.1016/j.cub.2020.11.037
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Nuclear Deformation Causes DNA Damage by Increasing Replication Stress

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Cited by 124 publications
(101 citation statements)
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“…As a result, lower lamin A levels promote faster transit through small constrictions requiring nuclear deformation. However, squeezing the nucleus through small confinements can result in DNA damage caused by both the deformation of the nucleus and rupture of nuclear envelope (Irianto et al, 2016a;Raab et al, 2016;Shah et al, 2020). Importantly, mutation or depletion of lamin A/C increases the frequency of nuclear envelope rupture and impairs the ability to efficiently repair and survive rupture events (Denais et al, 2016;Earle et al, 2020;Irianto et al, 2016a;Raab et al, 2016).…”
Section: Discussionmentioning
confidence: 99%
“…As a result, lower lamin A levels promote faster transit through small constrictions requiring nuclear deformation. However, squeezing the nucleus through small confinements can result in DNA damage caused by both the deformation of the nucleus and rupture of nuclear envelope (Irianto et al, 2016a;Raab et al, 2016;Shah et al, 2020). Importantly, mutation or depletion of lamin A/C increases the frequency of nuclear envelope rupture and impairs the ability to efficiently repair and survive rupture events (Denais et al, 2016;Earle et al, 2020;Irianto et al, 2016a;Raab et al, 2016).…”
Section: Discussionmentioning
confidence: 99%
“…Deformation of the nucleus during confined migration of MDA-MB-231 and BT-549 breast cancer cells or by mechanical compression of static cells can cause DNA damage in the S/G2 phase of the cell cycle without requiring mechanical rupture of the envelope (Shah et al, 2021). The DNA damage is likely due to a stalling of the DNA replication fork.…”
Section: Effect Of Compressive Stress On the Nucleusmentioning
confidence: 99%
“…Importantly, deformation of the nucleus, whether by migration through small pores, direct application of force, or spreading on stiff substrates, has been implicated in the loss of nuclear repair factors and accumulation of DNA damage [ 71 , 72 , 73 , 74 ]. Though increased DNA damage from deformation has not yet been documented in primary liver cells, nuclear deformation is increased in chronic liver diseases, raising the possibility that deformation is a mechanism of oncogenesis [ 61 , 75 ].…”
Section: Mechanically Induced Nuclear Deformation Activates Oncogenic Signaling and Increases Dna Damagementioning
confidence: 99%