DNA-dependent Protein Kinase (DNA-PK)

DNA-dependent protein kinase (DNA-PK) is a serine/threonine protein kinase complex that plays a central role in the repair of DNA double-strand breaks (DSBs) through the non-homologous end joining (NHEJ) pathway. It is also involved in V(D)J recombination, which is essential for immune system diversity. The complex consists of the catalytic subunit DNA-PKcs and the regulatory Ku heterodimer (Ku70 and Ku80). Activation requires binding to both the Ku heterodimer and exposed DNA ends at DSBs. DNA-PK is essential for repairing DSBs caused by ionizing radiation or other genotoxic stresses and is required for assembling antigen receptor genes in developing lymphocytes. It activates p53 following severe damage to trigger apoptosis if repair capacity is exceeded. Knockout or mutation leads to severe combined immunodeficiency (SCID). DNA-PK is also involved in mitosis regulation and possibly other cellular processes beyond canonical DSB repair pathways.

Other names

DNA-PKcs/Ku heterodimer complexPRKDCDNA-PK catalytic subunitKu70/Ku80

Inhibition of DNA-PK catalytic activity, preventing DNA repair and inducing apoptosis in cancer cells.