The expanding role of WEE1

Upon DNA damage, complex transduction cascades are unleashed to locate, recognise and repair affected lesions. The process triggers a pause in the cell cycle until the damage is resolved. Even under physiologic conditions, this deliberate interruption of cell division is essential to ensure orderly DNA replication and chromosomal segregation. WEE1 is an established regulatory protein in this vast fidelity-monitoring machinery. Its involvement in the DNA damage response and cell cycle has been a subject of study for decades. Emerging studies have also implicated WEE1 directly and indirectly in other cellular functions, including chromatin remodelling and immune response. The expanding role of WEE1 in pathophysiology is matched by the keen surge of interest in developing WEE1-targeted therapeutic agents. This review summarises WEE1 involvement in the cell cycle checkpoints, epigenetic modification and immune signalling, as well as the current state of WEE1 inhibitors in cancer therapeutics.