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

Sandeep Burma, David J. Chen

Research output: Contribution to journalReview article

178 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)909-918
Number of pages10
JournalDNA repair
Volume3
Issue number8-9
DOIs
StatePublished - Aug 1 2004

Keywords

  • Apoptosis
  • DNA double-strand breaks
  • DNA-dependent protein kinase
  • Innate immunity
  • Non-homologous end joining
  • Phosphorylation
  • Telomere maintenance

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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