4.3 Article

Roles of phosphatases in eukaryotic DNA replication initiation control

Journal

DNA REPAIR
Volume 118, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.dnarep.2022.103384

Keywords

Phosphatases; Replication initiation; Origin firing; Dephosphorylation; Checkpoint; Cell cycle

Funding

  1. AICR [10-0908]
  2. Wellcome Trust [107056/Z/15/Z]
  3. Cancer Research UK [C15873/A12700]
  4. AstraZeneca studentship [CR-000608]
  5. Wellcome Trust [107056/Z/15/Z] Funding Source: Wellcome Trust

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Protein phosphatases play a crucial role in DNA replication initiation by dephosphorylating replication initiation factors, ensuring timely and stable replication of the genome. Understanding the role of phosphatases may provide critical insights into cancer treatment, as many kinases involved in replication control are targets for new chemotherapies.
In eukaryotes, the phosphorylation of replication initiation factors by protein kinases is crucial to DNA repli-cation 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 repli-cation 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.

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