Buttrick, G. J., Meadows, J. C., Lancaster, T. C., Vanoosthuyse, V., Shepperd, L. A., Hoe, K.-L., Kim, D.-U., Park, H.-O., Hardwick, K. G. and Millar, Jonathan B. A.. (2011) Nsk1 ensures accurate chromosome segregation by promoting association of kinetochores to spindle poles during anaphase B. Molecular Biology of the Cell, Vol.22 (No.23). pp. 4486-4502. ISSN 1059-1524

Abstract

Type 1 phosphatase (PP1) antagonizes Aurora B kinase to stabilize kinetochore–microtubule attachments and to silence the spindle checkpoint. We screened for factors that exacerbate the growth defect of Δdis2 cells, which lack one of two catalytic subunits of PP1 in fission yeast, and identified Nsk1, a novel protein required for accurate chromosome segregation. During interphase, Nsk1 resides in the nucleolus but spreads throughout the nucleoplasm as cells enter mitosis. Following dephosphorylation by Clp1 (Cdc14-like) phosphatase and at least one other phosphatase, Nsk1 localizes to the interface between kinetochores and the inner face of the spindle pole body during anaphase. In the absence of Nsk1, some kinetochores become detached from spindle poles during anaphase B. If this occurs late in anaphase B, then the sister chromatids of unclustered kinetochores segregate to the correct daughter cell. These unclustered kinetochores are efficiently captured, retrieved, bioriented, and segregated during the following mitosis, as long as Dis2 is present. However, if kinetochores are detached from a spindle pole early in anaphase B, then these sister chromatids become missegregated. These data suggest Nsk1 ensures accurate chromosome segregation by promoting the tethering of kinetochores to spindle poles during anaphase B.

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