Regulation of the DNA-dependent protein kinase (DNA-PK) activity in eukaryotic cells

Biochimie. Jan-Feb 1999;81(1-2):117-25. doi: 10.1016/s0300-9084(99)80044-3.

Abstract

The DNA-dependent protein kinase (DNA-PK) is a trimeric nuclear serine/threonine protein kinase consisting of a large catalytic sub-unit and the Ku heterodimer that regulates kinase activity by its association with DNA. DNA-PK is a major component of the DNA double strand break repair apparatus, and cells deficient in one of its component are hypersensitive to ionizing radiation. DNA-PK is also required to lymphoid V(D)J recombination and its absence confers in mice a severe combined immunodeficiency phenotype. The purpose of this review is to summarize the current knowledge on the mechanisms that contribute to regulate DNA-PK activity in vivo or in vitro and relates them to the role of DNA-PK in cellular functions. Finally, the studies devoted to drug-inhibition of DNA-PK in order to enhance cancer therapy by DNA-damaging agents are presented.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Nuclear*
  • DNA Helicases*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / enzymology*
  • Ku Autoantigen
  • Mice
  • Nuclear Proteins / metabolism
  • Protein Binding
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*

Substances

  • Antigens, Nuclear
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Nuclear Proteins
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases
  • DNA Helicases
  • XRCC5 protein, human
  • Xrcc6 protein, human
  • Xrcc6 protein, mouse
  • Ku Autoantigen