Topoisomerase II (Topo II) performs topological modifications on double-stranded 
DNA molecules that are essential for chromosome condensation, resolution, and 
segregation. In mammals, G2 and metaphase cell cycle delays induced by Topo II 
poisons have been proposed to be the result of checkpoint activation in response 
to the catenation state of DNA. However, the apparent lack of such controls in 
model organisms has excluded genetic proof that Topo II checkpoints exist and 
are separable from the conventional DNA damage checkpoint controls. But here, we 
define a Topo II-dependent G2/M checkpoint in a genetically amenable eukaryote, 
budding yeast, and demonstrate that this checkpoint enhances cell survival. 
Conversely, a lack of the checkpoint results in aneuploidy. Neither DNA 
damage-responsive pathways nor Pds1/securin are needed for this checkpoint. 
Unusually, spindle assembly checkpoint components are required for the Topo II 
checkpoint, but checkpoint activation is not the result of failed chromosome 
biorientation or a lack of spindle tension. Thus, compromised Topo II function 
activates a yeast checkpoint system that operates by a novel mechanism.