Fig. 3.

Proposed mechanism for the activation and deactivation cycle of PI3KKs. PI3KKs are recruited to the site of damage by their respective activator complexes and they assume an open conformation that allows ATP catalysis and substrate phosphorylation. Once deactivated, the kinases are recycled, losing their affinity for the activator complexes, thereby physically leaving the site of damage in a closed conformation. Kinase-dead proteins are likely stuck on the DNA, impeding the proper repair of the DNA lesion