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Genetic 'tag team' keeps cells on cycle
Date:5/7/2008

enally successful. But now, with genome technologies, we have the opportunity to look at the dynamics of all the genes at the same time.

In this case, they evaluated the activity of about 6,000 genes over time in mutant yeast cells that lacked functional cyclins.

Under the old models, the parade of gene activity should have come to an abrupt halt without cyclin. Instead, while the yeast cells outwardly showed signs of the disruption and stopped dividing, nearly 70 percent of the periodic genes within them continued to turn on and off right on schedule.

The result doesnt mean that cyclins arent important, Haase said, but there is certainly more to the story.

Haases team now thinks that many cell cycle activities are driven by a series of transcription factors (genes that switch other genes on and off), acting one after another. Transcription factor one turns on the genes under its control along with transcription factor two; transcription factor two turns on its set of genes plus transcription factor three, and so on. The last transcription factors in the series then go back to turn on the first, starting the whole cycle over again.

Mathematical models constructed by the team showed that the waves of activity driven by such a network could provide a very robust oscillator even without cyclins, Haase said.

In fact, cyclins themselves are among the genes targeted by this transcription-activating tag team. Those cyclins are also known to influence the behavior of the transcription factors in the network. Therefore, Haase suggests that precise control over the cell cycle is ultimately achieved through the joint effort of the transcription factor network and cyclins. In other words, the two keep each other in line, which explains how cell division usually manages to persevere over a wide range of conditions.

When the cell cycle fails, one of the most devastating outcomes is cancer, he said. Obviously, if t
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Contact: Kendall Morgan
kendall.morgan@duke.edu
919-684-2850
Duke University
Source:Eurekalert

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