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Key mechanism in genetic inheritance during cell division identified

le fibers are woven together to form a highly flexible cytoskeleton in biological cells that gives shape to cell walls and other structures, and controls the transportation of substances in and out of a cell. During cell division (mitosis), the microtubule fibers disassemble and reform into spindles across which duplicate sets of chromosomes line up. During this phase, it is critical that the spindles maintain their structural integrity so that they can segregate a single copy of each chromosome to each daughter cell. After which, the microtubules again disassemble and reform back into skeletal systems for the two new daughter cells. It has been determined, through the genetic research of Barnes and Drubin, among others, that kinetochores must bind to a microtubule spindle to avoid the gain or loss of chromosomes by each of the daughter cells. How this works, however, was unknown.

To find answers, the Berkeley researchers used a purified, reconstituted Dam1 complex, obtained from genetically engineered E. coli bacteria, and compared its effects on microtubules in vitro to the effects caused by certain Dam1 mutants. Their analysis shed new light on the structural nature of the kinetochore-microtubule interface, and may provide a biochemical explanation for the role of kinetochores in maintaining chromosome segregation during mitosis.

"Our studies indicate that the Dam1 rings are formed by longitudinal self-assembly of multiple copies of the Dam1 complex upon the microtubule surface," the authors state in their Molecular Cell paper. "Although the presence of microtubules strongly facilitates the oligomerization process, ring assembly seems to be an intrinsic property of the Dam1 complex, as we have been able to induce self-assembly into rings in the absence of microtubules."

The formation of rings around the microtubules by the purified Dam1 complex that the Berkeley collaborators observed has not been reported for any other
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
1-Feb-2005


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