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bioRxiv · 10.1101/2020.02.25.962613

The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment

Legal, T.·Hayward, D.·Gluszek-Kustusz, A.·BLACKBURN, E.·Spanos, C.·Rappsilber, J.·Gruneberg, U.·Welburn, J. P.
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Abstract

During cell division, misaligned chromosomes are captured and aligned by motors before their segregation. The CENP-E motor is recruited to polar unattached kinetochores, to facilitate chromosome alignment. The spindle checkpoint protein BubR1 has been reported as a CENP-E interacting partner, but to what extent, if at all, BubR1 contributes to CENP-E localization at kinetochores, has remained controversial. Here we define the molecular determinants that specify the interaction between BubR1 and CENP-E. The basic C-terminal helix of BubR1 is necessary but not sufficient for CENP-E interaction, while a minimal key acidic patch on the kinetochore-targeting domain of CENP-E, is also essential. We then demonstrate that BubR1 is required for the recruitment of CENP-E to kinetochores to facilitate chromosome alignment. This BubR1-CENP-E axis is critical to align chromosomes that have failed to congress through other pathways and recapitulates the major known function of CENP-E. Overall, our studies define the molecular basis and the function for CENP-E recruitment to BubR1 at kinetochores during mammalian mitosis.

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Legal, T., Hayward, D., Gluszek-Kustusz, A., BLACKBURN, E., Spanos, C., Rappsilber, J., Gruneberg, U., Welburn, J. P.. 2020-02-26. The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment. https://doi.org/10.1101/2020.02.25.962613

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