Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 25645366.
- Also identified by DOI 10.1111/acel.12258 and PMC identifier 4364828.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- DNA Damage
- Intracellular Signaling Peptides and Proteins
- Lamin Type A