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

2017; Elsevier BV; Volume: 66; Issue: 6 Linguagem: Inglês

10.1016/j.molcel.2017.05.015

1097-4164

Andrew N. Blackford, Stephen P. Jackson,

Carcinogens and Genotoxicity Assessment

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.