Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks

Doug W. Chan, Benjamin Ping Chi Chen, Sheela Prithivirajsingh, Akihiro Kurimasa, Michael D. Story, Jun Qin, David J. Chen

Research output: Contribution to journalArticle

356 Scopus citations

Abstract

Nonhomologous end-joining (NHEJ) is the predominant pathway that repairs DNA double-strand breaks (DSBs) in mammalian cells. The DNA-dependent protein kinase (DNA-PK), consisting of Ku and DNA-PK catalytic subunit (DNA-PKcs), is activated by DNA in vitro and is required for NHEJ. We report that DNA-PKcs is autophosphorylated at Thr2609 in vivo in a Ku-dependent manner in response to ionizing radiation. Phosphorylated DNA-PKcs colocalizes with both γ-H2AX and 53BP1 after DNA damage. Mutation of Thr2609 to Ala leads to radiation sensitivity and impaired DSB rejoining. These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ.

Original languageEnglish (US)
Pages (from-to)2333-2338
Number of pages6
JournalGenes and Development
Volume16
Issue number18
DOIs
StatePublished - Sep 15 2002

Keywords

  • Autophosphorytation
  • DNA damage response
  • DNA-PK
  • DNA-PKcs
  • Ionizing radiation
  • Ku
  • Nonhomologous end-joining
  • Radiation sensitivity

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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