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Title: Functional analysis of the budding yeast Bub1 kinase
Author: Fernius, Josefin
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Bub1 is a conserved protein kinase that plays an essential role in the spindle checkpoint. The role of the Bub1 kinase activity remains elusive, and it is controversial whether it is required for spindle checkpoint arrest. In this study we use budding yeast as a model system to analyse the role of the Bub1 kinase domain, using a bub1ΔK allele lacking the C-terminal kinase domain. We show that bub1ΔK cells are able to initiate and maintain a mitotic arrest induced by microtubule de-polymerising drugs and kinetochore defects. Despite this, these cells display significant sensitivity to microtubule drugs and we show that this is because they are unable to accurately recover from spindle damage and mis-segregate their chromosomes at high rates. This phenotype is reminiscent of sgo1Δ cells in mitosis, and we show that Bub1 kinase is required for accurate localization of Sgo1 to kinetochores in metaphase. We then demonstrate that both Bub1 kinase and Sgo1 are required for efficient chromosome bi-orientation, and we suggest that this is due to inability to detect a lack of tension at the kinetochores. Finally, we propose that Bub1 kinase targets Sgo1 protein to kinetochores to ensure efficient chromosome bi-orientation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available