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Analysis of Borealin-mediated Centromere Targeting of the Chromosomal Passenger Complex

Bekier, Michael Edward, II
http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404730367

Abstract Details

2014, Doctor of Philosophy, University of Toledo, Biology (Cell-Molecular Biology).
The Chromosomal Passenger Complex (CPC) localizes to centromeres and monitors inter-kinetochore tension to activate the mitotic checkpoint and ensure faithful segregation of chromosomes during mitosis. The CPC subunit Borealin is implicated in centromere targeting of the complex, yet the details of targeting are not completely understood. We have used a combination of Borealin structure-function analysis, chemical genetics, FRAP, and an inducible FKBP dimerization system to investigate centromere targeting and function of the CPC. We provide evidence that Borealin dimerization plays two crucial roles in CPC targeting during mitosis. First, Borealin suppresses dynamic exchange at inner centromeres via dimerization of the CPC where slow exchange at centromeres is required for optimal CPC function. Second, the central region of Borealin targets the dimerized CPC to a region near kinetochores enabling feedback with Bub1 and activation of the mitotic checkpoint. The existence of a pool of CPC near kinetochores suggests that error correction is more complicated than predicted from the Aurora B phosphorylation gradient model. The critical role of Borealin dimerization in both inner centromere and kinetochore targeting of the CPC may simply result from a doubling of CPC interactions with its centromere and kinetochore receptors. Finally, we provide preliminary evidence that the CPC directly regulates Bub1 kinase activity at kinetochores, which is essential for localization of the CPC.
William Taylor, Dr. (Advisor)
Song-Tao Liu, Dr. (Committee Member)
Malathi Krishnamurthy, Dr. (Committee Member)
John Bellizzi, Dr. (Committee Member)
Ivana de la Serna, Dr. (Committee Member)
107 p.
Biology
Centromere; Checkpoint; Mitosis; Kinetochore; Chromosome

Recommended Citations

Citations

  • Bekier, II, M. E. (2014). Analysis of Borealin-mediated Centromere Targeting of the Chromosomal Passenger Complex [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404730367

    APA Style (7th edition)

  • Bekier, II, Michael. Analysis of Borealin-mediated Centromere Targeting of the Chromosomal Passenger Complex. 2014. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404730367.

    MLA Style (8th edition)

  • Bekier, II, Michael. "Analysis of Borealin-mediated Centromere Targeting of the Chromosomal Passenger Complex." Doctoral dissertation, University of Toledo, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1404730367

    Chicago Manual of Style (17th edition)

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© 2014, all rights reserved.
This open access ETD is published by University of Toledo and OhioLINK.