Role of DNA-PK in the cellular response to DNA double-strand breaks

DNA Repair (Amst). Aug-Sep 2004;3(8-9):909-18. doi: 10.1016/j.dnarep.2004.03.021.

Abstract

The DNA-dependent protein kinase (DNA-PK) plays a critical role in DNA double-strand break (DSB) repair and in V(D)J recombination. DNA-PK also plays a very important role in triggering apoptosis in response to severe DNA damage or critically shortened telomeres. Paradoxically, components of the DNA-PK complex are present at the mammalian telomere where they function in capping chromosome ends to prevent them from being mistaken for double-strand breaks. In addition, DNA-PK appears to be involved in mounting an innate immune response to bacterial DNA and to viral infection. As DNA-PK localizes very rapidly to DNA breaks and phosphorylates itself and other damage-responsive proteins, it appears that DNA-PK serves as both a sensor and a transducer of DNA-damage signals. The many roles of DNA-PK in the mammalian cell are discussed in this review with particular emphasis on recent advances in our understanding of the phosphorylation events that take place during the activation of DNA-PK at DNA breaks.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • DNA / chemistry
  • DNA Damage*
  • DNA Repair*
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins / physiology*
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / physiology*
  • Recombination, Genetic
  • Sequence Homology, Amino Acid
  • Telomere / ultrastructure
  • Threonine / chemistry
  • VDJ Recombinases / metabolism

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • XRCC4 protein, human
  • Threonine
  • DNA
  • DNA-Activated Protein Kinase
  • PRKDC protein, human
  • Protein-Serine-Threonine Kinases
  • VDJ Recombinases