Integrative structure modelling was applied to understand how auto-phosphorylation of the ABCDE cluster in DNA-PKcs can occur. We used crosslinking restraints to assign sequence to structurally unassigned helices in DNA-PKcs s in the largely disordered region containing the ABCDE cluster. Our final model positions the ABCDE cluster at the end of the second helices, suggesting that phosphorylation occurs through trans-auto-phosphorylation, or through a large conformational change in the disordered region for cis-auto-phosphorylation.