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Molecule tracking reveals mechanism of chromosome separation in dividing cells
Date:3/6/2009

sis Club led by Sue Biggins at the Fred Hutchinson Cancer Research Center.

To understand how the kinetochore functions, the scientists sought to uncover the basis for its most fundamental behavior: attaching microtubules. The most puzzling aspect of this attachment, according to the researchers, is that the kinetochore has to be strong yet dynamic. It has to keep a grip on the microtubule filaments even as they add and remove their subunits.

"This ability," the researchers said, "allows the kinetochore to harness microtubule shortening and lengthening to drive the movement of chromosomes."

The same coupling behavior is found in living things from yeast cells to humans, indicating that it was conserved during evolution as a good way of getting the job done.

The question is how this mechanism works. Previous studies implicated a large, multiprotein complex, Ndc80, as a direct contact point between kinetochores and microtubules. However, researchers had only a static view of the complex. The UW researchers used special techniques to manipulate and track the activity of the complex in a laboratory set-up.

The researchers were able to show that the Ndc80 complex was indeed capable of forming dynamic, load-bearing attachments to the tips of the microtubules, probably by forming an array of individually weak microtubule binding elements that rapidly bind and unbind, but with a total energy large enough to hold on. The mechanism will produce a molecular friction that resists translocation of the microtubule through the attachment site. Other scientists have dubbed the mechanism a "slip clutch."

This kind of coupler, the researchers added, is able to remain continuously attached to the microtubule tip during both its assembly and disassembly phases. The coupler also can harness the energy released during disassembly to produce mechanical force. Coupling may depend on positively charged areas on the complex that intera
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Contact: Leila Grau
leilag@u.washington.edu
206-685-0381
University of Washington
Source:Eurekalert

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