Safeguarding entry into mitosis: the antephase checkpoint

Abstract

Maintenance of genomic stability is needed for cells to survive many rounds of division throughout their lifetime. Key to the proper inheritance of intact genome is the tight temporal and spatial coordination of cell cycle events. Moreover, checkpoints are present that function to monitor the proper execution of cell cycle processes. For instance, the DNA damage and spindle assembly checkpoints ensure genomic integrity by delaying cell cycle progression in the presence of DNA or spindle damage, respectively. A checkpoint that has recently been gaining attention is the antephase checkpoint that acts to prevent cells from entering mitosis in response to a range of stress agents. We review here what is known about the pathway that monitors the status of the cells at the brink of entry into mitosis when cells are exposed to insults that threaten the proper inheritance of chromosomes. We highlight issues which are unresolved in terms of our understanding of the antephase checkpoint and provide some perspectives on what lies ahead in the understanding of how the checkpoint functions.

FIG. 1.

Cell cycle checkpoint pathways impinging upon the cell division cycle. The cell division cycle is monitored throughout by various checkpoints, including the DNA replication (blue box) and DNA damage (red box) checkpoints, as well as the spindle assembly checkpoint (gray box). In addition, the antephase checkpoint (green box) plays an important role in preventing mitotic entry in the presence of various stress conditions (see text).

FIG. 2.

Key players at the antephase checkpoint. As cells progress from G₂ into mitosis, there is a phase between these phases called antephase where chromosome condensation is reversible. The antephase appears to depend upon both p38 and CHFR for reversing chromosome condensation when the cells are exposed to stress agents, including spindle damage and low temperature.