When the homologous template is unavailable, the break ends are directly ligated through nonhomologous end joining repair. The initial step in NHEJ repair is the recognition and binding of the Ku70/80 heterodimer to the DSB . Subsequently, Ku serves as a scaffold to bring the other NHEJ factors to the damage site, including DNA-PKcs, XRCC4, DNA ligase IV, XRCC4-like factor (XLF) and/or ATM and ATR . Interestingly, the order of the sequential recruitment of these factors to the DSB mediated by the Ku heterodimer is quite flexible . Upon binding, Ku-DNA-PKcs or XRCC-XLF can bridge and stabilize DSB ends by protecting them from non-specific processing which may lead to chromosome aberrations. The next step is to make the ends ligatable by removing the damaged or mismatched nucleotides at DSB ends. Many enzymes, including PNKP, Artemis and Ku itself, have been reported responsible for processing DNA ends for the NHEJ pathway [21–23]. The ultimate step in NHEJ is gap filling by DNA polymerase and ligation of the broken ends by DNA Ligase IV whose activity can be stimulated by XRCC4 .