Open AccessLamin B1 sequesters 53BP1 to control its recruitment to DNA damage
Author(s) -
Laure Etourneaud,
Angela Moussa,
Emilie Rass,
Diane Genet,
Simon Willaume,
Caroline Chabance-Okumura,
Paul Wanschoor,
Julien Picotto,
Benoît Thézé,
Jordane Dépagne,
Xavier Veaute,
Eléa Dizet,
Didier Busso,
Aurélia Barascu,
Lamya Irbah,
Thierry Kortulewski,
Anna Campalans,
Catherine Le Chalony,
Sophie ZinnJustin,
Ralph Scully,
Gaëlle Pennarun,
Pascale Bertrand
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abb3799
Subject(s) - lamin , dna damage , dna , microbiology and biotechnology , biology , chemistry , genetics , nucleus
Double-strand breaks (DSBs) are harmful lesions and a major cause of genome instability. Studies have suggested a link between the nuclear envelope and the DNA damage response. Here, we show that lamin B1, a major component of the nuclear envelope, interacts directly with 53BP1 protein, which plays a pivotal role in the DSB repair. This interaction is dissociated after DNA damage. Lamin B1 overexpression impedes 53BP1 recruitment to DNA damage sites and leads to a persistence of DNA damage, a defect in nonhomologous end joining and an increased sensitivity to DSBs. The identification of interactions domains between lamin B1 and 53BP1 allows us to demonstrate that the defect of 53BP1 recruitment and the DSB persistence upon lamin B1 overexpression are due to sequestration of 53BP1 by lamin B1. This study highlights lamin B1 as a factor controlling the recruitment of 53BP1 to DNA damage sites upon injury.