A machine to accurately control chromosomal separation

University of Washington (UW) researchers are helping to understand a nano-scale machine that can separate chromosomes before cell division and could provide insight into chromosomal diseases, like Down Syndrome.

Called a spindle, the apparatus looks like a tiny wool-spinner with thin strands of microtubules sticking out. It lengthens and shortens microtubules, which is thought to help separate chromosome pairs.

Understanding how this machine accurately and evenly divides genetic material will help understand some cancers and birth defects, like Down Syndrome or Trisomy 18, which result from an uneven distribution of chromosomes.

A team led by UW scientists recently reported on the workings of a key component of this process: the kinetochore, a site on each chromosome that mechanically couples to spindle fibres.

"Kinetochores 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 scientists sought to uncover how the kinetochore attaches to microtubules — particularly puzzling, since the kinetochore has to keep a grip on the microtubule filaments even as they add and remove their subunits.

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

The same coupling behaviour is found in organisms ranging from yeast cells to humans, indicating that it was conserved during evolution as a successful way of getting the job done.

Based on their findings, the scientists propose arrays of large multiprotein complexes, called Ndc80, supply the combination of plasticity and strength that allows kinetechores to hold on loosely but not let go of the tips of the microtubules.

The researchers published their study 6 March in the journal Cell.