University of Washington (UW) researchers are helping to write the operating manual for the nano-scale machine that separates chromosomes before cell division. The apparatus is called a spindle because it looks like a tiny wool-spinner with thin strands of microtubules or spindle fibers sticking out. The lengthening and shortening of microtubules is thought to help push and pull apart chromosome pairs.
Understanding how this machine accurately and evenly divides genetic material is essential to learning why its parts sometimes fail. Certain cancers or birth defects, like Down syndrome or Trisomy 18, result from an uneven distribution of chromosomes.
In a study published March 6 in the journal Cell, a team led by UW scientists reports on the workings of a key component of this machine. Named a kinetochore, it is a site on each chromosome that mechanically couples to spindle fibers.
"Kineochores are also regulatory hubs," the researchers noted. "They control chromosome movements through the lengthening and shortening of the attached microtubules. They sense and correct errors in attachment. They emit a "wait" signal until the microtubules properly attach." Careful control over microtubules, they added, is vital for accurate splitting of the chromosomes.
The lead researchers on the study were Andrew F. Powers and Andrew D. Frank from the UW Department of Physiology and Biophysics and Daniel R. Gestaut, from the UW Department of Biochemistry. The senior authors of the study were Charles "Chip" Asbury, assistant professor, and Linda Wordeman, associate professor, both of physiology and biophysics and both members of the UW Center for Cell Dynamics; and Trisha Davis, professor of biochemistry, and director of the Yeast Resource Center.
Asbury is known for research on molecular machines and motors, Wordeman for work on chromosome movement, and Davis for studies of spindle poles. All are part of the Seattle Mito
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University of Washington