DOC_PIKK_1

DNA damage response pathways involve three major groups of evolutionarily conserved proteins that act together to translate the signal of damaged DNA into responses of cell cycle arrest and DNA repair. These groups comprise sensor proteins that recognize damaged DNA directly or indirectly, transducer proteins - typically PIKKs such as ATM, ATR and DNA-PKcs - that relay and amplify the damage signal, and effector proteins that control cell cycle progression, chromatin restructuring and DNA repair. Recruitment of DNA damage-associated PIKKs to DNA lesions is thought to be a principal step in their activation and in their function in checkpoint signalling and DNA repair. Although these PIKKs have an affinity for DNA, recruitment to DNA lesions is facilitated by specific partner proteins. For example, recruitment of ATR to single-stranded DNA (ssDNA) requires ATRIP and DNA-PKcs recruitment to DNA double-strand breaks (DSBs) is mediated by the Ku70-Ku80 heterodimer.