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

345 Citations (Scopus)

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

Fingerprint

DNA-Activated Protein Kinase
Double-Stranded DNA Breaks
Catalytic Domain
DNA
Radiation Tolerance
Ionizing Radiation
DNA Damage
Phosphorylation
Mutation

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. / Chan, Doug W.; Chen, Benjamin Ping Chi; Prithivirajsingh, Sheela; Kurimasa, Akihiro; Story, Michael D.; Qin, Jun; Chen, David J.

In: Genes and Development, Vol. 16, No. 18, 15.09.2002, p. 2333-2338.

Research output: Contribution to journalArticle

Chan, Doug W. ; Chen, Benjamin Ping Chi ; Prithivirajsingh, Sheela ; Kurimasa, Akihiro ; Story, Michael D. ; Qin, Jun ; Chen, David J. / Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. In: Genes and Development. 2002 ; Vol. 16, No. 18. pp. 2333-2338.
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