Abstract
During cell division all chromosomes must be segregated accurately to each daughter cell. Errors in this process give rise to aneuploidy, which leads to birth defects and is implicated in cancer progression. The spindle checkpoint is a surveillance mechanism that ensures high fidelity of chromosome segregation by inhibiting anaphase until all kinetochores have established bipolar attachments to spindle microtubules. Bub1 kinase is a core component of the spindle checkpoint, and cells lacking Bub1 fail to arrest in response to microtubule drugs and precociously segregate their DNA. The mitotic role(s) of Bub1 kinase activity remain elusive, and it is controversial whether this C-terminal domain of Bub1p is required for spindle checkpoint arrest. Here we make a detailed analysis of budding yeast cells lacking the kinase domain (bub1ΔK). We show that despite being able to arrest in response to microtubule depolymerisation and kinetochore-microtubule attachment defects, bub1ΔK cells are sensitive to microtubule drugs. This is because bub1ΔK cells display significant chromosome mis-segregation upon release from nocodazole arrest. bub1ΔK cells mislocalise Sgo1p, and we demonstrate that both the Bub1 kinase domain and Sgo1p are required for accurate chromosome biorientation after nocodazole treatment. We propose that Bub1 kinase and Sgo1p act together to ensure efficient biorientation of sister chromatids during mitosis.
Highlights
The fidelity of chromosome segregation is dependent upon correct bipolar attachment of sister chromatids to the spindle microtubules
We demonstrate that the Bub1 kinase domain acts to target Sgo1 to budding yeast centromeres, and that both of these proteins are required for efficient biorientation of chromosomes in yeast mitosis
We propose that this is because the mutant cells fail to respond to kinetochores that are not under tension, and that they are unable to correct syntelic attachments where both sister chromatids attach to microtubules from the same spindle pole
Summary
The fidelity of chromosome segregation is dependent upon correct bipolar attachment of sister chromatids to the spindle microtubules (for review see [1]). These attachments are mediated through complex, molecular machines called kinetochores, which assemble at the centromere of each chromosome (for reviews see [2,3]). One of the most important is the spindle checkpoint, which is a surveillance system that tightly regulates the metaphase-to-anaphase transition It ensures that all kinetochores have established proper bipolar ( known as amphitelic) attachments, where sister kinetochores are attached to microtubules emanating from opposite spindle pole bodies (SPBs), before anaphase is initiated [3,6,7]. When the spindle checkpoint is active, the APC/C is inhibited, Securin levels remain high, and anaphase onset is delayed
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