Time as a danger signal promoting G1 arrest after mitosis
Time is a danger signal directing potentially damaged mitotic cells to p53- dependent G1 arrest.
Mouse double minute homologue 2 (MDM2) functions as a molecular timer monitoring the length of mitosis.
If MDM2 drops below a threshold concentration at the end of mitosis, p53 is stabilised in G1 daughter cells, triggering cell cycle arrest through p21 induction.
USP28–53BP1 stopwatch complexes reinforce p53-dependent G1 arrest, potentially by antagonising MDM2 ubiquitination of p53.
Loss of the mitotic timer pathway enables proliferation of damaged or otherwise genomically unstable cells.
https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(25)00126-6
