One way to preserve a rare book is to lock it away from all potential sources of damage. Of course, an inaccessible book is also of little use, and the paper and ink will continue to degrade with age in any case. Like a book, the information stored in our DNA needs to be read, but it is also subject to continuous assault and therefore needs to be protected. In this Review, we examine how the replication stress response that is controlled by the kinase ataxia telangiectasia and Rad3-related (ATR) senses and resolves threats to DNA integrity so that the DNA remains available to read in all of our cells. We discuss the multiple data that have revealed an elegant yet increasingly complex mechanism of ATR activation. This involves a core set of components that recruit ATR to stressed replication forks, stimulate kinase activity and amplify ATR signalling. We focus on the activities of ATR in the control of cell cycle checkpoints, origin firing and replication fork stability, and on how proper regulation of these processes is crucial to ensure faithful duplication of a challenging genome.

中文翻译：

---

必需的激酶ATR：确保忠实复制具有挑战性的基因组

保存稀有书籍的一种方法是将其锁定在远离所有潜在损害源的位置。当然，一本难以接近的书也几乎没有用，无论如何纸张和墨水都会随着年龄的增长而继续退化。就像一本书一样，需要读取存储在我们DNA中的信息，但是它也受到不断的攻击，因此需要受到保护。在这篇综述中，我们研究了由共济失调毛细血管扩张症和Rad3相关（ATR）控制的复制应激反应如何感测和解决对DNA完整性的威胁，从而使DNA仍可在我们所有细胞中读取。我们讨论了多种数据，这些数据揭示了一种优雅而又日益复杂的ATR激活机制。这涉及一组核心组件，这些组件可以将ATR募集到有压力的复制分支中，刺激激酶活性并放大ATR信号传导。我们专注于ATR在控制细胞周期检查点，起源激发和复制叉稳定性方面的活动，以及对这些过程的适当调节对于确保忠实地复制具有挑战性的基因组至关重要。