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Dissecting the signalling cascade in the vertebrate spindle assembly checkpoint

Final Activity Report Summary - KINETOCHECK (Dissecting the signalling cascade in the vertebrate spindle assembly checkpoint)

Accurate chromosome separation is highly controlled by a checkpoint, because an error during this step cannot be corrected. If this checkpoint is deficient, cells with abnormal chromosome number will be produced, which is a hallmark of cancer. In order to study this process, we studied 3 proteins situated at the anchoring point of the chromosome to the separation machinery, a beautiful cellular structure called the mitotic spindle.

I studied how CENP-E is properly localised, and I found by which domain it binds to its partner BubR1, which is strictly correlated with its proper localization. This suggests that direct binding of CENP-E to BubR1 is required for the correct localisation of CENP-E. I have also identified several modifications (by phosphorylation) of CENP-E and Mps1, and I am currently pursuing my work to understand the mechanistic details of CENP-E regulation by Mps1.