Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

TY - JOUR

T1 - Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage

AU - Gibbs-Seymour, Ian

AU - Markiewicz, Ewa

AU - Bekker-Jensen, Simon

AU - Mailand, Niels

AU - Hutchison, Christopher J

N1 - © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - 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.

AB - 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.

U2 - 10.1111/acel.12258

DO - 10.1111/acel.12258

M3 - Journal article

C2 - 25645366

SN - 1474-9718

VL - 14

SP - 162

EP - 169

JO - Aging Cell

JF - Aging Cell

IS - 2

ER -