Fig. 1.

NHEJ temporal and spatial organisation of the structural components as stages, scaffolds and strings. A) Temporal organisation of NHEJ. Ku70 is coloured in purple and Ku80 is in yellow, DNA-PKcs is coloured in green. Ku70/80 and DNA-PKcs, the first two NHEJ components assembling at the DSBs, act as stages for downstream factors. Later, non-catalytic proteins, such as XRCC4 (X-ray repair cross-complementing protein 4), XLF (XRCC4-like factor) and PAXX (paralog of XRCC4 and XLF), act as scaffolds for DNA-end synapsis and ligation and can participate along with proteins such as Artemis and APLF (Aprataxin and PNK-like factor) with intrinsically disordered regions that can act as strings to hold multiple NHEJ components. Other accessory proteins with enzyme activity, such as PNKP (polynucleotide kinase/phosphatase) and DNA polymerases, may also join the end-processing step. DNA ligase IV, the only ligase involved in NHEJ, catalyses the final ligation; B) Spatial organisation of NHEJ including stages, scaffolds and strings together with accessory proteins. DNA-protein interactions are shown as black arrows while protein-protein interactions are shown as purple arrows.