Figure 5. Proposed model of the interaction of Akt1 with the NHEJ pathway.

Autophosphorylated active DNA-PKcs phosphorylates Akt1 at S473 at the DNA damage site. Activated Akt1 is now able to stabilize nearby D-NHEJ complexes via phosphorylation of UBE2S at its T152 leading to an enhanced association of UBE2S with Ku70 and the repair complex³⁹. At a later stage of the repair Akt1 might introduce the dissociation of the D-NHEJ complex by phosphorylation of XLF at its phosphorylation site T181¹⁷. The phosphorylation of XLF triggers the dissociation of XLF from the DNA ligase IV/XRCC4 complex as a final step of the DSB repair. Furthermore, Akt1 functions as a switch upon genotoxic stress between cell cycle arrest/survival or apoptosis.