Taming the Spindle for Containing the Chromosomes

Abstract

Checkpoint controls are critical for coordination of cell cycle events, especially during exposure to perturbations or stresses. The DNA replication checkpoint is activated in S phase in response to replication stresses that impede fork progression. Mec1 and Rad53 are critical effectors of this control pathway; they maintain the integrity of stalled replication forks and prevent premature segregation of unreplicated chromosomes. It has long been thought that the checkpoint inhibits precocious segregation of chromosomes by preventing early onset of mitosis. However, recent evidence suggests that the replication checkpoint thwarts untimely chromosome separation not by inhibiting mitotic entry but by directly regulating spindle dynamics. These findings raise a number of issues which may require a revisit to the well-trodden territories of cell cycle regulation.