FIGURE 1.

Dominant two-ended DSB repair pathways. (Left) cNHEJ is the dominant pathway for repairing two-ended DSBs. cNHEJ acts on blunt or minimally processed ends bound by Ku70/Ku80 and DNA-PKcs. Short gaps are filled and ends are ligated to complete repair, typically with small insertions or deletions at the repair junction (Right) HR initiates with 5′-3′ resection and binding of ssDNA by RPA, which is replaced by RAD51 in a reaction mediated by BRCA2 and RAD51 paralogs. The RAD51 nucleoprotein filament invades homologous duplex DNA, assisted by RAD54, RAD54B and other factors. RAD51 dissociates and the invading end is extended and then released allowing pairing to ssDNA on the opposite side of the DSB. Gaps are filled and ends ligated to complete accurate DSB repair.