Roles of phosphatases in eukaryotic DNA replication initiation control

In eukaryotes, the phosphorylation of replication initiation factors by protein kinases is crucial to DNA replication control. This control ensures that the genome is only copied once per cell cycle and that replication occurs in a timely manner, minimising stress. Indeed, uncontrolled DNA replication initiation causes genome instability and occurs early on in cancer development. Here we discuss the known roles of protein phosphatases in replication initiation as part of cell cycle control and the DNA damage response. We highlight how dephosphorylation ensures that DNA replication initiation events are robust, dynamic, and spatially regulated. As many kinases involved in replication control are targets for new chemotherapies, an understanding of the role of phosphatases may give critical insights into cancer treatment.