Time as a danger signal promoting G1 arrest after mitosis.

Abstract

Cell cycle checkpoints preventing the replication and inheritance of damaged DNA are crucial for maintaining genome stability and stopping the growth of damaged cells. Canonical checkpoints do this by preventing passage between cell cycle phases until damage has been repaired, or by promoting cell cycle exit. Herein we review checkpoint integration between cell cycle phases, specifically findings showing that extended spindle assembly checkpoint surveillance in mitosis is a danger signal triggering G1 cell cycle arrest. Evidence linking mitotic delays induced by activation of the spindle assembly checkpoint with positive and negative regulators of the G1 DNA damage checkpoint target p53 is discussed, with a focus on time-dependent changes to a p53-binding deubiquitinating complex USP28-53BP1 and the p53 ubiquitin-ligase mouse double minute homologue 2 (MDM2), respectively.