29 May

System that controls division of cells resembles a mosaic

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The protein complex that the cells of animals, plants, and fungi use to control cell division was created long ago from at least 40 different proteins. This could explain the overwhelming success of all cells with a cell nucleus, according to the group of Geert Kops at the Hubrecht Institute and the group of Berend Snel at Utrecht University. Their results were published in the scientific journal PNAS.

“You might think that a fungus more closely resembles bacteria than it does us”, says Geert Kops, cell biologist at the Hubrecht Institute. “But that’s not the case. In contrast to the prokaryotic bacterial cells, the eukaryotic cells of fungi, plants, and animals all have a nucleus that stores the DNA.”

Although both types of cells can replicate their DNA and then divide it among two new daughter cells, the systems by which prokaryotes and eukaryotes distribute the DNA among the daughter cells are completely different. Eukaryotes use what is known as a ‘kinetochore’; a protein complex that might have been crucial in their success.

Microtubule threads (red) pull the chromosomes (blue) to both sides of the nucleus. Each chromosome contains a kinetochore (green dots). Credit: Banafseh Etemad, © Hubrecht Institute

Kinetochore starting shot for metaphase
“The genetic material is recorded in the DNA in the chromosome,” says Geert Kops. “During cell division, both chromatids – the two copies of a chromosome – contain a protein complex that resembles a fairground grappling hook. This kinetochore ensures that all of the chromosomes form an orderly line in the middle of the nucleus. The cell only divides after all of the kinetochores have reported that they have completed their tasks. This is the start signal for the metaphase, in which the chromatids are pulled apart at the exact same time.”

Berend Snel, theoretical biologist at Utrecht University (UU), describes what this looks like when it occurs under a microscope. “At first, there’s one last chromosome that isn’t in position in the middle of the nucleus. And then, once that last chromosome has joined the rest, all of a sudden all of the chromatids let go and move to their own half.”

No intermediate form, and therefore indispensable
The kinetochore in every eukaryotic cell on Earth has a complex structure, while prokaryotic cells don’t have a kinetochore. In evolutionary theory, the absence of simple intermediate forms is an indication of the protein’s importance. Berend Snel: “That makes it even more relevant for us to find out how the protein complex developed. All of the kinetochores on Earth today should come from the same ancestor.”

The kinetochore, a mosaic of at least 40 different proteins

Data mining
Former PhD students Eelco Tromer (Hubrecht Institute) and Jolien van Hooff (UU) were able to unravel its lineage by combining an improved, more sensitive method for searching for comparable DNA sequences – and therefore relationships – with new insights into the composition of the protein complex. Berend Snel: “We used 3D structures of the kinetochore’s sub-complexes that had been published by other scientists. By data mining through that information, we were able to determine how the system evolved. The protein complex appears to be a mosaic of at least 40 primordial proteins, which have been duplicated over and over again.”

To me, the kinetochore is like the black hole of eukaryotic cell division.

Black hole of cell division
The publication provides insight into the development of life. Geert Kops, Hubrecht Institute: “An accurate, coordinated division is essential to a cell’s success. To me, the kinetochore is like the black hole of eukaryotic cell division. We would very much like to know how the system developed, and how it functions in every organism on Earth. This work will contribute to that understanding.”

Mosaic origin of the eukaryotic kinetochore.
 Eelco Tromer*, Jolien J.E. van Hooff*, Geert J.P.L. Kops^ en Berend Snel^. PNAS 2019.
*equal contribution, ^co-last author



Geert Kops is group leader at the Hubrecht Institute, professor of Molecular Tumor Cell Biology at the University Medical Center Utrecht and Oncode Investigator.


Berend Snel is professor in bioinformatics at Utrecht University and leads the Evolutionary Genomics and Integrative Bioinformatics group.