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DNA damage alters nuclear mechanics through chromatin reorganization

dos Santos, Ália, Cook, Alexander W, Gough, Rosemarie E, Schilling, Martin, Olszok, Nora A, Brown, Ian R., Wang, Lin, Aaron, Jesse, Martin-Fernandez, Marisa L, Rehfeldt, Florian, and others. (2020) DNA damage alters nuclear mechanics through chromatin reorganization. Nucleic Acids Research, 49 (1). pp. 340-353. ISSN 1362-4962. (doi:10.1093/nar/gkaa1202) (KAR id:98987)

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AbstractDNA double-strand breaks drive genomic instability. However, it remains unknown how these processes may affect the biomechanical properties of the nucleus and what role nuclear mechanics play in DNA damage and repair efficiency. Here, we have used Atomic Force Microscopy to investigate nuclear mechanical changes, arising from externally induced DNA damage. We found that nuclear stiffness is significantly reduced after cisplatin treatment, as a consequence of DNA damage signalling. This softening was linked to global chromatin decondensation, which improves molecular diffusion within the organelle. We propose that this can increase recruitment for repair factors. Interestingly, we also found that reduction of nuclear tension, through cytoskeletal relaxation, has a protective role to the cell and reduces accumulation of DNA damage. Overall, these changes protect against further genomic instability and promote DNA repair. We propose that these processes may underpin the development of drug resistance.

Item Type: Article
DOI/Identification number: 10.1093/nar/gkaa1202
Additional information: ** Article version: VoR ** From Crossref journal articles via Jisc Publications Router ** History: epub 16-12-2020; issued 16-12-2020; ppub 11-01-2021. ** Licence for VoR version of this article starting on 17-12-2020:
Uncontrolled keywords: Genetics
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
Funders: Royal Society (
Medical Research Council (
Science and Technology Facilities Council (
SWORD Depositor: JISC Publications Router
Depositing User: JISC Publications Router
Date Deposited: 09 Dec 2022 12:59 UTC
Last Modified: 12 Dec 2022 10:39 UTC
Resource URI: (The current URI for this page, for reference purposes)
Rehfeldt, Florian:
Toseland, Christopher P:
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