DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product

KO Hartley, D Gell, GCM Smith, H Zhang, N Divecha… - Cell, 1995 - cell.com
KO Hartley, D Gell, GCM Smith, H Zhang, N Divecha, MA Connelly, A Admon…
Cell, 1995cell.com
DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-stranded break
repair and V (D) J recombination, comprises a DNA-targeting component called Ku and an-
460 kDa catalytic subunit, DNA-PKc~. Here, we describe the cloning of the DNA-PK~, cDNA
and show that DNA-PI~, falls into the phosphatidylinositol (PI) 3-kinase family. Biochemical
assays, however, indicate that DNA-PK phosphorylates proteins but has no detectable
activity toward lipids. Strikingly, DNA-PI~ s is most similar to PI kinase family members …
Summary
DNA-dependent protein kinase (DNA-PK), which is involved in DNA double-stranded break repair and V (D) J recombination, comprises a DNA-targeting component called Ku and an-460 kDa catalytic subunit, DNA-PKc~. Here, we describe the cloning of the DNA-PK~, cDNA and show that DNA-PI~, falls into the phosphatidylinositol (PI) 3-kinase family. Biochemical assays, however, indicate that DNA-PK phosphorylates proteins but has no detectable activity toward lipids. Strikingly, DNA-PI~ s is most similar to PI kinase family members involved in cell cycle control, DNA repair, and DNA damage responses. These include the FKBP12-rapamycin-binding proteins Torlp, Tor2p, and FRAP, S. pombe rad3, and the product of the ataxia telangiectasia gene, mutations in which lead to genomic instability and predisposition to cancer. The relationship of these proteins to DNA-PK~ s provides important clues to their mechanisms of action.
cell.com