THE DNA-DEPENDENT PROTEIN-KINASE, DNA-PK - 10 YEARS AND NO ENDS IN SIGHT

The phenomenon of DNA-dependent protein phosphorylation was first desc ribed little over 10 years ago. Since then a DNA-dependent protein kin ase, DNA-PK, has been purified from human cells and many of its bioche mical properties have been characterized. DNA-PK is composed of a larg e catalytic subunit, DNA-PKcs, and a DNA-targeting protein, Ku. When a ssembled on a suitable DNA molecule, the DNA-PK holoenzyme acts as a s erine/threonine protein kinase that in vitro phosphorylates many DNA b inding and non-binding proteins and transcription factors. Recent gene tic studies point strongly to functions in DNA double-strand break rep air and V(D)J recombination. In addition, biochemical studies suggest a role in the regulation of transcription. Here we discuss, from a his torical perspective, the events leading up to our current understandin g of the function of DNA-PK, including recent results from our own stu dies suggesting the involvement of DNA-PK in apoptosis and. in viral i nfection of human cells.