title: Nsk1 ensures accurate chromosome segregation by promoting association of kinetochores to spindle poles during anaphase B.
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.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom.
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Buttrick
authors.forename: John C
authors.initials: JC
authors.lastname: Meadows
authors.forename: Theresa C
authors.initials: TC
authors.lastname: Lancaster
authors.forename: Vincent
authors.initials: V
authors.lastname: Vanoosthuyse
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Shepperd
authors.forename: Kwang-Lae
authors.initials: KL
authors.lastname: Hoe
authors.forename: Dong-Uk
authors.initials: DU
authors.lastname: Kim
authors.forename: Han-Oh
authors.initials: HO
authors.lastname: Park
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Hardwick
authors.forename: Jonathan B A
authors.initials: JB
authors.lastname: Millar
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004398:Dyneins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D055550:Protein Stability; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; C571108:Nsk1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C502092:Dis2 protein, S pombe; D010749:Phosphoprotein Phosphatases; C439269:Clp1 protein, S. pombe; D017027:Protein Tyrosine Phosphatases; D004398:Dyneins