Figure 1.

DSB induction and NHEJ repair pathway: (a) DSB initiates phosphorylation by activated phophotidylinositol-3 kinase-like kinases (PIKKs) and phosphorylation of H2AX (γH2AX) for cascade signaling; (b) RNA polymerase I-based local transcription inhibition in the DSB proximity, RNA polymerase II activation for damage-induced RNA generation, and the recruitment of NHEJ or HR repair machinery; (c) KU heterodimer binding at broken ends for NHEJ repair initiation and deubiquitylation of the Ku80 subunit; (d) DNA-PKcs autophosphorylates and then phosphorylates LIG4. LINP1 and LRIK are non-coding RNAs that stabilize the KU–DNA complex; (e) recruitment of XLF, APLF, and PAXX; (f) end processing by Artemis nuclease and other end processing molecules, and gap filling by polymerases; (g) LIG4 ligate-processed ends assisted with XRCC4, PAXX and XLF.