ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Blackford, AN
Jackson, SP
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.
Description
Keywords
Animals, Antineoplastic Agents, Ataxia Telangiectasia Mutated Proteins, Calcium-Binding Proteins, Cell Nucleus, DNA Damage, DNA Repair, Enzyme Activation, History, 20th Century, History, 21st Century, Humans, Models, Molecular, Neoplasms, Phosphorylation, Protein Conformation, Protein Kinase Inhibitors, Signal Transduction, Structure-Activity Relationship, Tumor Suppressor Protein p53
Journal Title
Molecular Cell
Conference Name
Journal ISSN
1097-2765
1097-4164
1097-4164
Volume Title
66
Publisher
Cell Press
Publisher DOI
Sponsorship
Cancer Research UK (18796)
Wellcome Trust (206388/Z/17/Z)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)
Wellcome Trust (206388/Z/17/Z)
Wellcome Trust (092096/Z/10/Z)
Cancer Research Uk (None)