title: Polyploids require Bik1 for kinetochore-microtubule attachment.
abstract: The attachment of kinetochores to spindle microtubules (MTs) is essential for maintaining constant ploidy in eukaryotic cells. Here, biochemical and imaging data is presented demonstrating that the budding yeast CLIP-170 orthologue Bik1is a component of the kinetochore-MT binding interface. Strikingly, Bik1 is not required for viability in haploid cells, but becomes essential in polyploids. The ploidy-specific requirement for BIK1 enabled us to characterize BIK1 without eliminating nonhomologous genes, providing a new approach to circumventing the overlapping function that is a common feature of the cytoskeleton. In polyploid cells, Bik1 is required before anaphase to maintain kinetochore separation and therefore contributes to the force that opposes the elastic recoil of attached sister chromatids. The role of Bik1 in kinetochore separation appears to be independent of the role of Bik1 in regulating MT dynamics. The finding that a protein involved in kinetochore-MT attachment is required for the viability of polyploids has potential implications for cancer therapeutics.
authors.affiliation: Department of Pediatric Oncology, The Dana-Farber Cancer Institute, The Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lin
authors.forename: P
authors.initials: P
authors.lastname: de Carvalho
authors.forename: D
authors.initials: D
authors.lastname: Kho
authors.forename: C Y
authors.initials: CY
authors.lastname: Tai
authors.forename: P
authors.initials: P
authors.lastname: Pierre
authors.forename: G R
authors.initials: GR
authors.lastname: Fink
authors.forename: D
authors.initials: D
authors.lastname: Pellman
mesh_terms: D001665:Binding Sites; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000502:physiology*; D008870:Microtubules / Q000502:physiology*; D009363:Neoplasm Proteins; D011123:Polyploidy; D011485:Protein Binding; D011993:Recombinant Fusion Proteins; D012441:Saccharomyces cerevisiae
chemical_list: D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; C076744:cytoplasmic linker protein 170