@article{6995695b9e4b4e41ab7d4d6bbca672ec,
title = "The C-terminal helix of BubR1 is essential for CENP-E-dependent chromosome alignment",
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 (also known as BUB1B) has been reported as a CENP-E interacting partner, but the extent to which 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, and 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 for alignment of 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.",
keywords = "CENP-E, Kinetochore, Microtubule, Mitosis, Motor",
author = "Thibault Legal and Daniel Hayward and Agata Gluszek-Kustusz and Blackburn, {Elizabeth A.} and Christos Spanos and Juri Rappsilber and Ulrike Gruneberg and Welburn, {Julie P.I.}",
note = "Funding Information: The Wellcome Centre for Cell Biology is supported by core funding from the Wellcome Trust (203149), a multi-user equipment grant (101527) for the Edinburgh Protein Production Facility and a multi-user equipment grant (108504) for the Orbitrap Fusion Lumos. Funding Information: J.R. is supported by a Wellcome Trust Senior Research Fellowship (103139). J.P.I.W. is supported by a Wellcome Trust Senior Reseach Fellowship (207430). D.H. was supported by a Medical Research Council Senior Non-Clinical Fellowship (MR/K006703/1) awarded to U.G. Open access funding provided by University of Edinburgh. Deposited in PMC for immediate release. Funding Information: The Wellcome Centre for Cell Biology is supported by core funding from the Wellcome Trust (203149), a multi-user equipment grant (101527) for the Edinburgh Protein Production Facility and a multi-user equipment grant (108504) for the Orbitrap Fusion Lumos. J.R. is supported by a Wellcome Trust Senior Research Fellowship (103139). J.P.I.W. is supported by a Wellcome Trust Senior Reseach Fellowship (207430). D.H. was supported by a Medical Research Council Senior Non-Clinical Fellowship (MR/K006703/1) awarded to U.G. Open access funding provided by University of Edinburgh. Deposited in PMC for immediate release. Publisher Copyright: {\textcopyright} 2020. Published by The Company of Biologists Ltd | Journal of Cell Science (2020) 133, jcs246025. doi:10.1242/jcs.246025",
year = "2020",
month = aug,
doi = "10.1242/jcs.246025",
language = "English",
volume = "133",
journal = "Journal of Cell Science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "16",
}