BRCA1 and 53BP1 in DSB repair. a) Repair of replication associated breaks requires HR. 53BP1 blocks resection of the one-ended break in BRCA1 deficient cells, preventing repair via HR. The breaks are either left unrepaired or repaired via NHEJ using other random DNA ends, which leads to chromosomal rearrangements and genomic instability. In the absence of 53BP1, resection of the DNA ends can take place, allowing faithful repair via HR. b) IR induced two ended DSBs are mainly repaired via NHEJ, however part of the breaks is repaired via HR or alternative end-joining (alt-EJ). Repair via HR or alt-EJ increases when classical NHEJ is impaired by a mutation in one of the core NHEJ genes or 53BP1.