Editor: Stefan Westermann, A1

Date: 08/02/2021

Summary:
In our bodies several hundred billions of cells divide each day to replenish tissues and maintain important functions of our organism. The proliferation of cells requires that their genetic blueprint, packaged in the form of chromosomes, is precisely copied and distributed between the daughter cells during each cell division. Crucial for this process is the correct attachment of chromosomes to microtubule filaments of the mitotic spindle, mediated by a large protein complex termed the kinetochore. The microtubule filaments of the cell can be viewed as long ropes and the chromosomes somehow have to grab and hold on to the end of these ropes during each cell division. Work from A01 (Westermann) and A04 (Gatsogiannis) have revealed new aspects of how chromosomes bind correctly to microtubule filaments. The kinetochores of the eukaryotic model system baker’s yeast contain a large ring-forming complex, called Dam1, which embraces the microtubules and thereby helps to bind to the end of the cellular ropes. Through biochemical reconstitution the process of ring assembly could be recapitulated in the test tube by A01. Electron microscopy analysis by A04 then helped to explain how another protein, called Bim1, connects the links of the Dam1 chain and helps to assemble the full ring complex. With these important insights, further structural and functional aspects of ring assembly can be studied in the future. This may allow to explain how cells manage to pass on their genetic information with such high precision and determine what aspects of the process go awry in cells with abnormal chromosome numbers frequently observed in different types of cancer.

Publication:

Dudziak A, Engelhard L, Bourque C, Klink BU, Rombaut P, Kornakov N, Jänen K, Herzog F, Gatsogiannis C, Westermann S.
Phospho-regulated Bim1/EB1 interactions trigger Dam1c ring assembly at the budding yeast outer kinetochore.
EMBO J. 2021 Sep 15;40(18):e108004.

Link to the publication