Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage
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Lamins A/C have been implicated in DNA damage response pathways. We show that the DNA repair protein 53BP1 is a lamin A/C binding protein. In undamaged human dermal fibroblasts (HDF), 53BP1 is a nucleoskeleton protein. 53BP1 binds to lamins A/C via its Tudor domain, and this is abrogated by DNA damage. Lamins A/C regulate 53BP1 levels and consequently lamin A/C-null HDF display a 53BP1 null-like phenotype. Our data favour a model in which lamins A/C maintain a nucleoplasmic pool of 53BP1 in order to facilitate its rapid recruitment to sites of DNA damage and could explain why an absence of lamin A/C accelerates aging.
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Loss of lamin A/C is associated with the induction of cellular senescence through DNA-damage sensing pathways.
“Loss of lamin A/C is associated with the induction of cellular senescence through DNA-damage sensing pathways [45].”
From Early onset senescence and cognitive impairment in a murine model of repeated mTBI (2021) · cites this paper as [45]
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- Authors
- Gibbs-Seymour, I., Markiewicz, E., Bekker-Jensen, S., Mailand, N., & Hutchison, C. J.
- Affiliations
- School of Biological and Biomedical Sciences; Durham University; Mountjoy Science Park Durham DH1 3LE UK
- Durham University (GB)
- Ubiquitin Signaling Group; Department of Disease Biology; Novo Nordisk Foundation Center for Protein Research; University of Copenhagen; Copenhagen DK-2200 Denmark
- University of Copenhagen (DK)
- Corresponding author
- Markiewicz, Ewa
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2015-01-23
- Volume
- 14
- Issue
- 2
- Pages
- 162-169
- ISSN
- 1474-9718 (ISSN-L)
- PMC
- PMC4364828
- OpenAlex
- W1970417373
- Cited by
- 90
- References
- 35
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 7 · 2022: 12 · 2021: 11 · 2020: 7 · 2019: 10 · 2018: 9 · 2017: 6 · 2016: 3 · 2015: 1
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Aging Cell (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- FedUni ResearchOnline (Federation University Australia) (submittedVersion, cc-by-nc-nd)
- Funders
- Biotechnology and Biological Sciences Research Council (BB/KO19260/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- lamin A/C, 53BP1, DNA damage response, Tudor domain, nucleoskeleton, DNA repair, dermal fibroblasts, aging
- MeSH terms
- Tumor Suppressor p53-Binding Protein 1, DNA Damage, DNA Repair, Fibroblasts, Humans, Protein Binding, Protein Structure, Tertiary, Lamin Type A, Cell Line, Tumor, Intracellular Signaling Peptides and Proteins, HEK293 Cells
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