25 June 2018

A corona for chromosomes

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A new publication of the Kops group in the journal Nature Cell Biology describes their discovery of a way in which chromosomes can capture the molecular ropes (a.k.a. microtubules) that pull them apart during cell division.

When a cell divides, its most important task is to make sure that each daughter cell receives the right complement of chromosomes. The wrong complement can kill cells or set them on a path towards becoming a cancer cell. Cells achieve this by connecting chromosomes to microtubules via a specialized chromosomal structure known as the kinetochore. A challenge for the cell is to get all chromosomes correctly attached to microtubules in a timely manner. Studies from the 1960s showed that during the period they need to make the first contacts with microtubules, kinetochores have a large, extra layer termed the ‘corona’. The corona is only present in the earliest phases of cell division, but disappears once microtubule connections are made.

Using various cell imaging, biochemical and biophysical techniques, the Kops group now discovered the molecular nature of this corona, and how it assembles in those early phases of cell division. Using that knowledge, they were able to show that the corona is like Velcro for microtubules, allowing kinetochores to stick to microtubules as soon as they are in proximity of one another. They furthermore revealed how the corona disappears in later phases of cell division, and showed that this is important to prevent errors in distributing the chromosomes to the daughter cells. The corona is therefore essential for the initial capture of microtubules, and correct regulation of the corona is important in preventing the chromosome segregation errors often seen in cancer cells.

Paper: http://www.nature.com/articles/s41556-018-0130-3

Image: a cell preparing to divide: DNA in blue, kinetochores in red, coronas in green.

Geert Kops is group leader at the Hubrecht Institute and professor of Molecular Tumor Cell Biology at the University Medical Center Utrecht. His group is interested in the processes that ensure correct chromosome segregation during cell division. Errors in chromosome segregation can cause birth defects and embryonic lethality in humans and cause aneuploidy, the most common genetic alteration in tumors. The Kops group studies the signaling networks that regulate chromosome segregation, the evolution of cell division processes and the role of chromosomal instability in cancer.