Storchova Z, Becker J, Talarek N, Koegelsberger S, Pellman D

The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding ...

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yeast, but they become essential in cells with higher ploidy. We find that over-expression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosome passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Over-expression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 over-expression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization and does not affect Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B -independent function in establishment of biorientation. We found that Sgo1 over-expression rescues defects caused by metaphase inactivation of Mps1; and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of Aurora B - mediated pathway at the budding yeast kinetochore, and that both these pathways are required for the efficient turnover of syntelic attachments.

Date: Mar. 09, 2011

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