DNA-activated protein kinase (DNA-PK; EC 22.214.171.124) plays an important role in responding to agents and extracellular stress that threaten the DNA replication process. It is a nuclear protein serine/threonine kinase that must bind to DNA double-strand breaks (DSB) to be active. The nonhomologous end-joining (NHEJ) pathway is considered the main pathway for DSB repair in mammalian cells, and is initiated by binding of DNA-dependent protein kinase (DNA-PK) regulatory subunits to free DNA ends, followed by recruitment of the DNA-dependent kinase catalytic subunit protein (DNA-PKcs) to DSBs. This assembly results in DNA-PK kinase activation. The DNA-PK complex serves as a platform that holds both DNA ends together and orchestrates DNA processing and ligation.DNA-PK inhibiting Axon Ligands™ are also listed in the section of theDNA-damage response.
 ATM,ATR andDNA-PK: initiators of the cellular genotoxic stress responses. J Yang, Y Yu, H Hamrick, PJ Duerksen-Hughes. Carcinogenesis 2003, 24, 1571-1580.
 Essential role forDNA-PK-mediated phosphorylation of NR4A nuclear orphan receptors inDNA double-strand break repair. M. Malewicz et al. Genes & Dev. 2011, 25, 2031-2040.