The maintenance of genomic integrity relies on the coordination of a wide range of cellular processes and efficient repair of DNA damage. Since its discovery over two decades ago, the ATR kinase has been recognized as the master regulator of the circuitry orchestrating the cellular responses to DNA damage and replication stress. Recent studies reveal that ATR additionally functions in the unperturbed cell cycle through its control of replication fork speed and stability, replication origin firing, completion of genome duplication, and chromosome segregation. Here, we discuss several recently discovered mechanisms through which ATR safeguards genomic integrity during the cell cycle, from S phase to mitosis.

基因组完整性的维持依赖于广泛的细胞过程的协调和 DNA 损伤的有效修复。自二十多年前发现以来，ATR 激酶已被公认为是协调细胞对 DNA 损伤和复制压力反应的电路的主要调节器。最近的研究表明，ATR 通过控制复制叉的速度和稳定性、复制起点激发、基因组复制的完成和染色体分离，在未受干扰的细胞周期中另外发挥作用。在这里，我们讨论了几种最近发现的机制，通过这些机制，ATR 在细胞周期（从 S 期到有丝分裂）期间保护基因组完整性。