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Slow escape from mitosis

Even when mitotic cells lack a spindle, cyclin (bottom panels) slowly fades away. RIEDER/ELSEVIER

Cells with a defective spindle get delayed—stuck in a mitotic checkpoint—but eventually escape mitosis. In vertebrate cells, say Daniela Brito and Conly Rieder (Wadsworth Center, New York State Department of Health, Albany, NY), that escape is a gradual limp rather than a sudden exit.

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.

Reference:

Brito, D.A., and C.L. Rieder. 2006. Curr. Biol. 16:1194–1200.[CrossRef][Medline]

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 860K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?