Gibbs-Seymour Ian, Markiewicz Ewa, Bekker-Jensen Simon, Mailand Niels, Hutchison Christopher J
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.
Aging Cell. 2015 Apr;14(2):162-9. doi: 10.1111/acel.12258. Epub 2015 Jan 23.
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.
核纤层蛋白A/C与DNA损伤反应途径有关。我们发现DNA修复蛋白53BP1是一种核纤层蛋白A/C结合蛋白。在未受损的人皮肤成纤维细胞（HDF）中，53BP1是一种核骨架蛋白。53BP1通过其Tudor结构域与核纤层蛋白A/C结合，而DNA损伤会消除这种结合。核纤层蛋白A/C调节53BP1的水平，因此缺乏核纤层蛋白A/C的HDF表现出类似53BP1缺失的表型。我们的数据支持一种模型，即核纤层蛋白A/C维持53BP1的核质池，以便于其快速募集到DNA损伤部位，这可以解释为什么缺乏核纤层蛋白A/C会加速衰老。
