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

Thibault Legal, Daniel Hayward, Agata Gluszek-Kustusz, Elizabeth Blackburn, Christos Spanos, Juri Rappsilber, Ulrike Gruneberg, Julie P I Welburn

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article numberjcs246025
Number of pages11
JournalJournal of Cell Science
Volume133
Issue number16
DOIs
Publication statusPublished - 25 Aug 2020

Keywords

  • CENP-E
  • motor
  • kinetochore
  • mitosis
  • microtubule

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