Bub1 And CENP-U Recruit Plk1 To Ensure Accurate Chromosome Segregation

Mitosis is the basis of biological reproduction and development,it is an important process of cell division,through which cells increase the number of cells and transmit1 of genetic matter.Mitosis is a precision regulated process in which any minor error would lead to defects in chromosome alignment and segregation.Bub1 is required for the kinetochore/centromere localization of Polo-like kinase 1(Plk1)and Aurora B kinase,both are key regulators of mitotic chromosome segregation.Surprisingly,stable depletion of Bub1 by ?95% in human cells marginally affects whole chromosome segregation fidelity.We provide evidence that CENP-U,which is recruited to kinetochores by CENP-P and CENP-Q,is required to prevent chromosome mis-segregation in Bub1-depleted cells.Mechanistically,CENP-U and Bub1 redundantly recruit Plk1 to kinetochores to stabilize kinetochoremicrotubule attachments,thereby ensuring accurate chromosome segregation.Furthermore,unlike its budding yeast homolog,the CENP-U complex does not regulate centromeric localization of Aurora B.Importantly,depletion of Bub1 or CENP-U sensitizes cells to partial inhibition of the kinase activity of Plk1 but not Aurora B.Taken together,our findings provide mechanistic insight into the regulation of kinetochore function,which may have implications for targeted treatment of cancer cells harboring mutations down-regulating Bub1 or the CENP-U complex.