Established and Emerging Roles of the DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs)

  • Edward J. Bartlett
  • Susan P. Lees-MillerEmail author
Part of the Cancer Drug Discovery and Development book series (CDD&D)


The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a large polypeptide of over 4000 amino acids with serine/threonine protein kinase activity that is enhanced in the presence of double stranded DNA and the Ku70/80 heterodimer. The discovery of this DNA activated protein kinase activity led to investigation of its role in DNA double-strand break repair and DNA-PKcs was shown to play important roles in repair of ionizing radiation-induced DNA double strand breaks and V(D)J recombination through the non-homologous end joining (NHEJ) pathway. However, recently, additional roles for DNA-PKcs in mitosis, transcription and cell migration have been suggested. Here, we review the structure, established and emerging roles of DNA-PKcs and its potential as a target for cancer therapy.


DNA-PKcs Non-homologous end joining DNA damage repair Double strand break V(D)J recombination 



Work in the authors laboratory is supported by the Canadian Institute of Health Research, the Cancer Research Society and the Engineered Air Chair in Cancer Research. EB was supported by a University of Calgary Eyes High Post-Doctoral Fellowship.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology and Robson DNA Science Centre, Arnie Charbonneau Cancer InstituteUniversity of CalgaryCalgaryCanada
  2. 2.Sir William Dunn School of PathologyUniversity of OxfordOxfordUK

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