Reference: Makrantoni V and Stark MJ (2009) Efficient chromosome biorientation and the tension checkpoint in Saccharomyces cerevisiae both require Bir1. Mol Cell Biol 29(16):4552-62

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Abstract

Accurate chromosome segregation requires capture of sister kinetochores by microtubules from opposite spindle poles prior to initiation of anaphase, a state termed chromosome bi-orientation. In the budding yeast Saccharomyces cerevisiae, the conserved protein kinase Ipl1 kinase (Aurora B in metazoans) is critical for ensuring correct chromosomal alignment. Ipl1 associates with its activator Sli15 (INCENP), Nbl1 (Borealin) and Bir1 (Survivin), but while Sli15 clearly functions with Ipl1 to promote chromosome bi-orientation, the role of Bir1 has been uncertain. Using a temperature-sensitive bir1 mutant (bir1-17) we show that Bir1 is needed to permit efficient chromosome bi-orientation. However, once established, chromosome bi-orientation is maintained in bir1-17 cells at the restrictive temperature. Ipl1 is partially delocalized in bir1-17 cells and its protein kinase activity is markedly reduced under non-permissive conditions. bir1-17 cells arrest normally in response to microtubule depolymerization but fail to delay anaphase when sister kinetochore tension is reduced. Thus Bir1 is required for the 'tension checkpoint'. Despite their robust mitotic arrest in response to nocodazole, bir1-17 cells are hypersensitive to microtubule depolymerizing drugs and show a more severe bi-orientation defect on recovery from nocodazole treatment. The role of Bir1 may therefore become more critical when spindle formation is delayed.

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Journal Article
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Makrantoni V, Stark MJ
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