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A check on tension
Date:4/21/2013

oteins of the CPC, Aurora B kinase, is an enzyme that monitors that tension. Aurora B is expressed at high levels in many cancers and has long been a target for the development of cancer therapies.

Aurora B is essentially a molecular detector. "If the chromosomes are not under tension," says Desai, "Aurora B forces the rope to release the kinetochore and try attaching over and over again, until they achieve that correct, tense attachment."

The question is how? Aurora B is ordinarily found between the two kinetochores in a region of the chromosome that links the sister chromatids, known as the centromere. The prevailing model held that the microtubule ropes would pull themselves, and the kinetochores, away from Aurora B's reach, so that it cannot force the microtubule ropes to detach from their captive chromosomes. In other words, the location of Aurora B between the two kinetochore discs was thought to be central to its role as a monitor of the requisite tension. "This matter was thought settled," says Desai.

Yet, as Campbell and Desai show through their experiments, yeast cells engineered to carry a mutant CPC that can't be targeted to the centromere survive quite vigorously. They demonstrate that in such cells Aurora B instead congregates on the microtubule ropes. There, it somehow still ensures that the required tension is achieved on chromosomes before they are parceled out to daughter cells.

How precisely it does this remains unclear. Campbell and Desai provide evidence that the clustering of Aurora B on microtubules might be sufficient to activate its function. At the same time, they hypothesize, appropriate tension on the chromosome may induce structural changes in Aurora B's targets that make them resistant to its enzymatic activity. Campbell and Desai are now conducting experiments to test these ideas.


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Contact: Rachel Steinhardt
rsteinhardt@licr.org
212-450-1582
Ludwig Institute for Cancer Research
Source:Eurekalert

Page: 1 2

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