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

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Targeting the DNA Damage Response for Anti-Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology and Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada

    Edward J. Bartlett & Susan P. Lees-Miller

  2. Sir William Dunn School of Pathology, University of Oxford, Oxford, England, UK

    Edward J. Bartlett

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  1. Edward J. Bartlett
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  2. Susan P. Lees-Miller
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Correspondence to Susan P. Lees-Miller .

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  1. Vertex Pharmaceuticals (Europe) Ltd, Abingdon, Oxfordshire, United Kingdom

    John Pollard

  2. Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom

    Nicola Curtin

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Bartlett, E.J., Lees-Miller, S.P. (2018). Established and Emerging Roles of the DNA-Dependent Protein Kinase Catalytic Subunit (DNA-PKcs). In: Pollard, J., Curtin, N. (eds) Targeting the DNA Damage Response for Anti-Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-75836-7_12

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