DNA–dependent protein kinase in telomere maintenance and protection

This review focuses on DNA–dependent protein kinase (DNA–PK), which is the key regulator of canonical non–homologous end–joining (NHEJ), the predominant mechanism of DNA double–strand break (DSB) repair in mammals. DNA–PK consists of the DNA–binding Ku70/80 heterodimer and the catalytic subunit DNA–PKcs. They assemble at DNA ends, forming the active DNA–PK complex, which initiates NHEJ–mediated DSB repair. Paradoxically, both Ku and DNA–PKcs are associated with telomeres, and they play crucial roles in protecting the telomere against fusions. Herein, we discuss possible mechanisms and contributions of Ku and DNA–PKcs in telomere regulation.