53BP1 is a mediator of DNA damage response (DDR) and a tumor suppressor whose 
accumulation on damaged chromatin promotes DNA repair and enhances DDR 
signaling. Using foci formation of 53BP1 as a readout in two human cell lines, 
we performed an siRNA-based functional high-content microscopy screen for 
modulators of cellular response to ionizing radiation (IR). Here, we provide the 
complete results of this screen as an information resource, and validate and 
functionally characterize one of the identified 'hits': a nuclear pore component 
NUP153 as a novel factor specifically required for 53BP1 nuclear import. Using a 
range of cell and molecular biology approaches including live-cell imaging, we 
show that knockdown of NUP153 prevents 53BP1, but not several other DDR factors, 
from entering the nuclei in the newly forming daughter cells. This translates 
into decreased IR-induced 53BP1 focus formation, delayed DNA repair and impaired 
cell survival after IR. In addition, NUP153 depletion exacerbates DNA damage 
caused by replication stress. Finally, we show that the C-terminal part of 
NUP153 is required for effective 53BP1 nuclear import, and that 53BP1 is 
imported to the nucleus through the NUP153-importin-β interplay. Our data define 
the structure-function relationships within this emerging 
53BP1-NUP153/importin-β pathway and implicate this mechanism in the maintenance 
of genome integrity.