An extending ATR–CHK1 circuitry: the replication stress response and beyond

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.