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Mol Cell. 2017 Jun 15;66(6):801-817. doi: 10.1016/j.molcel.2017.05.015.

ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response.

Author information

1
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK; Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK; Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK. Electronic address: andrew.blackford@oncology.ox.ac.uk.
2
Wellcome Trust and Cancer Research UK Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK; Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK. Electronic address: s.jackson@gurdon.cam.ac.uk.

Abstract

In vertebrate cells, the DNA damage response is controlled by three related kinases: ATM, ATR, and DNA-PK. It has been 20 years since the cloning of ATR, the last of the three to be identified. During this time, our understanding of how these kinases regulate DNA repair and associated events has grown profoundly, although major questions remain unanswered. Here, we provide a historical perspective of their discovery and discuss their established functions in sensing and responding to genotoxic stress. We also highlight what is known regarding their structural similarities and common mechanisms of regulation, as well as emerging non-canonical roles and how our knowledge of ATM, ATR, and DNA-PK is being translated to benefit human health.

PMID:
28622525
DOI:
10.1016/j.molcel.2017.05.015
[Indexed for MEDLINE]
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