DNA double-strand breaks are typically repaired through either the high-fidelity 
process of homologous recombination (HR), in which BRCA1 plays a key role, or 
the more error-prone process of non-homologous end joining (NHEJ), which relies 
on 53BP1. The balance between NHEJ and HR depends, in part, on whether 53BP1 
predominates in binding to damage sites, where it protects the DNA ends from 
resection. The nucleoporin Nup153 has been implicated in the DNA damage 
response, attributed to a role in promoting nuclear import of 53BP1. Here, we 
define a distinct requirement for Nup153 in 53BP1 intranuclear targeting to 
damage foci and report that Nup153 likely facilitates the role of another 
nucleoporin, Nup50, in 53BP1 targeting. The requirement for Nup153 and Nup50 in 
promoting 53BP1 recruitment to damage foci induced by either etoposide or 
olaparib is abrogated in cells deficient for BRCA1 or its partner BARD1, but not 
in cells deficient for BRCA2. Together, our results further highlight the 
antagonistic relationship between 53BP1 and BRCA1, and place Nup153 and Nup50 in 
a molecular pathway that regulates 53BP1 function by counteracting 
BRCA1-mediated events.