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ATM, ATR, and DNA-PK: The trinity at the heart of the DNA damage response

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1016/j.molcel.2017.05.015

Authors


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Institution:
University of Oxford
Division:
MSD
Department:
Oncology
Sub department:
CRUK/MRC Ox Inst for Radiation Oncology
Role:
Author


More from this funder
Funding agency for:
Blackford, A
Grant:
C29215/A20772
C6946/A14492


Publisher:
Cell Press
Journal:
Molecular Cell More from this journal
Volume:
66
Issue:
6
Pages:
801-817
Publication date:
2017-06-15
Acceptance date:
2017-05-16
DOI:
ISSN:
1097-4164


Language:
English
Pubs id:
pubs:702140
UUID:
uuid:08865817-a929-480c-b0ab-8ce634ebaf16
Local pid:
pubs:702140
Source identifiers:
702140
Deposit date:
2017-06-30

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