<figcaption> Credit: © 2006 NATURE PUBLISHING GROUP</figcaption>

The cell cycle is generally considered a one way ticket to division. Recently, through chemical and genetic trickery, Gary Gorbsky at the Oklahoma Medical Research Foundation and colleagues reversed the process.1 They first triggered premature mitotic exit in Xenopus and human cells using inhibitors of cyclin-dependent kinase 1 (Cdk1). This normally also degrades the Cdk1 activator cyclin B. If the researchers next prevented cyclin B degradation or expressed non-degradable cyclin B and then washed out the Cdk1 inhibitors, the cells returned to metaphase. "You can actually see mitosis go backwards," says Faculty of 1000 member Claire Walczak at Indiana University in Bloomington.

"At the end of mitosis, several key substrates are degraded, which allows chromosome segregation and mitotic exit to proceed properly. However in this paper, by using a series of small molecule inhibitors that block such degradation they are able to reverse...

"This paper highlights the creative power of chemical inhibitors and how they can be utilized to temporally dissect a process. [The researchers] are now in a position to define which molecules are most critical in the process of mitotic exit reversal, which may set the stage for new approaches to blocking mitosis and thus halting cell proliferation."

1. T.A. Potapova et al. "The reversibility of mitotic exit in vertebrate cells." Nature, 440:954-8. April 13, 2006.

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