Understanding chromosome segregation during cell division

chromosome segregation
Yeast cells with their kinetochores fluorescently-labelled (pink/purple spots).

Peter Thorpe and Eva Herrero at the Francis Crick Institute have published research revealing that protein degradation pathways play a key role in making sure dividing cells end up with the right number of chromosomes.

The scientists found that protein degradation pathways control the levels of protein at the kinetochore – a key structure that helps segregate chromosomes during cell division. The findings have implications for understanding cancer, as many cancer cells have abnormal numbers of chromosomes caused by incorrect segregation during cell division.

Dr Thorpe explained: “As cells divide, their replicated chromosomes must be correctly allocated to the two new daughter cells. This is achieved by the kinetochore, which provides a physical link between the chromosomes and the microtubules that drive their movement. If chromosome separation fails, the resulting cells have an abnormal number of chromosomes. This state is called aneuploidy and is a hallmark of cancer cells.

“The regulation of the kinetochore is therefore of critical importance in maintaining the correct number of chromosomes in dividing cells. Since a number of cancer cells have overactive kinetochore genes, it has been proposed that an excess of kinetochore proteins can disrupt the normal assembly or maintenance of kinetochores.”

The researchers tested this idea in yeast cells by increasing the amount of a specific kinetochore protein. However they found no effect on the normal loading of kinetochore proteins.

Instead, they found that proteins called ubiquitin ligases play a role in maintaining the normal balance of the different kinetochore proteins by breaking down those that are not needed. This allows chromosomes to be correctly segregated into new cells as cells divide.

Dr Thorpe said: “Our work suggests that the overexpression of specific kinetochore genes, seen in some cancers, is not alone sufficient to cause problems for normal chromosome segregation.”

The paper, Synergistic Control of Kinetochore Protein Levels by Psh1 and Ubr2, is published in PLoS Genetics.