The multiprotein nuclear pore complex (NPC) controls molecular transport between the nucleus and the cytoplasm in interphase. Three nucleoporins (Nups) Nup153, Nup50 and Tpr form the nuclear basket on the nuclear side of the NPC. Besides their role in nucleocytoplasmic transport, these Nups have been linked to DNA transcription, replication and repair. For example, Nup153 aids the import of the DNA repair mediator 53BP1, which controls the non-homologous end joining pathway (NHEJ) in DNA double-strand repair (DSB). Now, Birthe Fahrenkrog and co-workers (p. 2306) set out to further assess the role of nuclear basket nucleoporins in DSB repair pathways. They show that Nup50, Nup153 and Tpr are all required for efficient NHEJ, with the latter two also being implicated in homologous recombination. Furthermore, when Nup153 is depleted from cells, the SUMO1 modification of 53BP1 is reduced and the SUMO sentrin-specific protease 1 (SENP1) is lost from NPCs. Interestingly, the artificial tethering of SENP1 to NPCs in cells depleted of Nup153 rescues sumoylation of 53BP1 and restores NHEJ. Taken together, the data establish a role for Nup153 in the regulation of the activity of the DNA repair factor 53BP1 by mediating the association of SENP1 with the NPC, which facilitates sumoylation of 53BP1 that is important for DSB repair by the NHEJ pathway.
