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J Cell Sci. 2017 Jul 15;130(14):2306-2316. doi: 10.1242/jcs.198390. Epub 2017 Jun 2.

Localisation of Nup153 and SENP1 to nuclear pore complexes is required for 53BP1-mediated DNA double-strand break repair.

Author information

1
Laboratory Biology of the Nucleus, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, Charleroi 6041, Belgium.
2
Laboratory Biology of the Nucleus, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, Charleroi 6041, Belgium bfahrenk@ulb.ac.be.

Abstract

The nuclear basket of nuclear pore complexes (NPCs) is composed of three nucleoporins: Nup153, Nup50 and Tpr. Nup153 has a role in DNA double-strand break (DSB) repair by promoting nuclear import of 53BP1 (also known as TP53BP1), a mediator of the DNA damage response. Here, we provide evidence that loss of Nup153 compromises 53BP1 sumoylation, a prerequisite for efficient accumulation of 53BP1 at DSBs. Depletion of Nup153 resulted in reduced SUMO1 modification of 53BP1 and the displacement of the SUMO protease SENP1 from NPCs. Artificial tethering of SENP1 to NPCs restored non-homologous end joining (NHEJ) in the absence of Nup153 and re-established 53BP1 sumoylation. Furthermore, Nup50 and Tpr, the two other nuclear basket nucleoporins, also contribute to proper DSB repair, in a manner distinct from Nup153. Similar to the role of Nup153, Tpr is implicated in NHEJ and homologous recombination (HR), whereas loss of Nup50 only affects NHEJ. Despite the requirement of all three nucleoporins for accurate NHEJ, only Nup153 is needed for proper nuclear import of 53BP1 and SENP1-dependent sumoylation of 53BP1. Our data support the role of Nup153 as an important regulator of 53BP1 activity and efficient NHEJ.

KEYWORDS:

53BP1; DNA damage response; Nuclear pore complex; Nucleoporin; Nup153; SENP1; SUMO

PMID:
28576968
DOI:
10.1242/jcs.198390
[Indexed for MEDLINE]
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