The temporary stalling of the cell cycle in a checkpoint gives the cell time to repair damage before continuing. Ted Weinert and Lee Hartwell gave this phenomenon its name, but “they never viewed a checkpoint as leading to a permanent arrest,” says Rieder.
Indeed, even in response to a problem that cannot be fixed, such as high levels of the anti-microtubule drug nocodazole, many cells do leak through the mitotic arrest. In yeast and perhaps flies, the escape occurs via phosphorylation of Cdk1 or induction of a Cdk1 inhibitor. This adaptation pathway turns off the Cdk1/cyclin B complex, whose activity defines mitosis.
A similar abrupt change was expected in vertebrate cells, via Cdk1 phosphorylation, induction of a Cdk1 inhibitor, or rapid degradation of cyclin B. “But it turns out it doesn't do any of these,” says Rieder. Instead, “human cells slowly degrade cyclin B over the course of time.”
This slow, proteasome-dependent degradation of cyclin B was required for nocodazole-treated cells to escape from mitosis. The spindle assembly checkpoint remained intact and active throughout. Thus Brito and Rieder believe that vertebrate cells do not turn on a specific adaptation pathway. Instead there is a constant low level of cyclin B degradation that eventually reduces cyclin B levels below that needed to maintain a mitotic state. In plants the resultant exit may allow a change in ploidy, although its utility in mammals is less clear.