The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight.
The phenomenon of DNA-dependent protein phosphorylation was first described little over 10 years ago. Since then a DNA-dependent protein kinase, DNA-PK, has been purified from human cells and many of its biochemical properties have been characterized. DNA-PK is composed of a large catalytic subunit, DNA-PKcs, and a DNA-targeting protein, Ku. When assembled on a suitable DNA molecule, the DNA-PK holoenzyme acts as a serine/threonine protein kinase that in vitro phosphorylates many DNA binding and non-binding proteins and transcription factors. Recent genetic studies point strongly to functions in DNA double-strand break repair and V(D)J recombination. In addition, biochemical studies suggest a role in the regulation of transcription. Here we discuss, from a historical perspective, the events leading up to our current understanding of the function of DNA-PK, including recent results from our own studies suggesting the involvement of DNA-PK in apoptosis and in viral infection of human cells.
Lees-Miller
S P
SP
Department of Biological Sciences, University of Calgary, AB, Canada. leesmill@acs.ucalgary.ca
D000818:Animals; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004789:Enzyme Activation; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D011995:Recombination, Genetic; D013045:Species Specificity; D013379:Substrate Specificity; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases