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  • Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation.

Bub1 and CENP-U redundantly recruit Plk1 to stabilize kinetochore-microtubule attachments and ensure accurate chromosome segregation.

Cell reports (2021-09-23)
Qinfu Chen, Miao Zhang, Xuan Pan, Xueying Yuan, Linli Zhou, Lu Yan, Ling-Hui Zeng, Junfen Xu, Bing Yang, Long Zhang, Jun Huang, Weiguo Lu, Tatsuo Fukagawa, Fangwei Wang, Haiyan Yan
RESUMEN

Bub1 is required for the kinetochore/centromere localization of two essential mitotic kinases Plk1 and Aurora B. Surprisingly, stable depletion of Bub1 by ∼95% in human cells marginally affects whole chromosome segregation fidelity. We show that CENP-U, which is recruited to kinetochores by the CENP-P and CENP-Q subunits of the CENP-O complex, is required to prevent chromosome mis-segregation in Bub1-depleted cells. Mechanistically, Bub1 and CENP-U redundantly recruit Plk1 to kinetochores to stabilize kinetochore-microtubule attachments, thereby ensuring accurate chromosome segregation. Furthermore, unlike its budding yeast homolog, the CENP-O complex does not regulate centromeric localization of Aurora B. Consistently, depletion of Bub1 or CENP-U sensitizes cells to the inhibition of Plk1 but not Aurora B kinase activity. Taken together, our findings provide mechanistic insight into the regulation of kinetochore function, which may have implications for targeted treatment of cancer cells with mutations perturbing kinetochore recruitment of Plk1 by Bub1 or the CENP-O complex.

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Cóctel de inhibidores de proteasas, for use with mammalian cell and tissue extracts, DMSO solution
Sigma-Aldrich
Anti-CENP-A Antibody, Upstate®, from rabbit