DNA-dependent protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase that is activated upon DNA damage generated by ionizing radiation or UV-irradiation. It is a three-protein complex consisting of a 470-kDa catalytic subunit (DNA-PKcs) and the regu-latory DNA binding subunits, Ku heterodimer (Ku70 and Ku80). Mouse and human cells deficient in DNA-PKcs are hypersensitive to ionizing radiation and de-fective in V(D)J recombination, suggesting a role for the kinase in double-strand break repair and recombi-nation. The Ku heterodimer binds to double-strand DNA breaks produced by either DNA damage or re-combination, protects DNA ends from degradation, orients DNA ends for re-ligation, and recruits its cata-lytic subunit and additional factors necessary for suc-cessful end-joining. DNA-PK is also involved in an early stage of damage-induced cell cycle arrest, how-ever, it remains unclear how the enzyme senses DNA damage and transmits signals to downstream gene(s) and proteins.

Keywords: DNA Damage, DSB Repair, DNA-PK, Damage Checkpoint