ATM、ATR 和 DNA-PK：DNA 损伤反应中的三位一体。

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

机构信息

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.

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.

出版信息

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

DOI:10.1016/j.molcel.2017.05.015

PMID:28622525

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.

摘要

在脊椎动物细胞中，DNA 损伤反应由三种相关激酶控制：ATM、ATR 和 DNA-PK。ATR 是这三种激酶中最后一个被鉴定的，自其克隆以来已经过去了 20 年。在此期间，我们对这些激酶如何调节 DNA 修复和相关事件的理解已经有了深刻的认识，尽管仍有一些重大问题尚未得到解答。在这里，我们提供了它们发现的历史视角，并讨论了它们在检测和应对遗传毒性应激方面的既定功能。我们还强调了它们在结构相似性和共同调控机制方面的已知内容，以及新兴的非典型作用，以及我们对 ATM、ATR 和 DNA-PK 的了解如何转化为造福人类健康。