title: Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.
abstract: 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.
authors: School of Biological and Biomedical Sciences, Durham University, Mountjoy Science Park, Durham, DH1 3LE, UK; Ubiquitin Signaling Group, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors: Ian
authors: I
authors: Gibbs-Seymour
authors: Ewa
authors: E
authors: Markiewicz
authors: Simon
authors: S
authors: Bekker-Jensen
authors: Niels
authors: N
authors: Mailand
authors: Christopher J
authors: CJ
authors: Hutchison
mesh_terms: D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000071857:Tumor Suppressor p53-Binding Protein 1
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C494847:LMNA protein, human; D034904:Lamin Type A; C498301:TP53BP1 protein, human; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: 53BP1; DNA damage response; laminopathy; lamins
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