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DNA damage alters nuclear mechanics through chromatin reorganization

Title data

dos Santos, Ália ; Cook, Alexander W. ; Gough, Rosemarie E. ; Schilling, Martin ; Olszok, Nora A. ; Brown, Ian ; Wang, Lin ; Aaron, Jesse ; Martin-Fernandez, Marisa L. ; Rehfeldt, Florian ; Toseland, Christopher P.:
DNA damage alters nuclear mechanics through chromatin reorganization.
In: Nucleic Acids Research. Vol. 49 (11 January 2021) Issue 1 . - pp. 340-353.
ISSN 1362-4962
DOI: https://doi.org/10.1093/nar/gkaa1202

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Abstract in another language

DNA 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.

Further data

Item Type: Article in a journal
Refereed: Yes
Institutions of the University: Faculties > Faculty of Mathematics, Physics und Computer Science > Department of Physics > Chair Experimental Physics I - Physics of Living Matter > Chair Experimental Physics I - Physics of Living Matter - Univ.-Prof. Dr. Matthias Weiss
Result of work at the UBT: No
DDC Subjects: 500 Science > 530 Physics
500 Science > 570 Life sciences, biology
Date Deposited: 23 Feb 2021 12:27
Last Modified: 23 Feb 2021 12:30
URI: https://eref.uni-bayreuth.de/id/eprint/63343