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dc.contributor.authorPagliuca, Cinzia
dc.contributor.authorDraviam, Viji M.
dc.contributor.authorMarco, Eugenio
dc.contributor.authorSorger, Peter Karl
dc.contributor.authorDe Wulf, Peter
dc.date.accessioned2011-02-18T16:19:35Z
dc.date.issued2009
dc.identifier.citationPagliuca, Cinzia, Viji M. Draviam, Eugenio Marco, Peter K. Sorger, and Peter De Wulf. 2009. Roles for the conserved Spc105p/Kre28p complex in kinetochore-microtubule binding and the spindle assembly checkpoint. PLoS ONE 4, no. 10: e7640.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:4727658
dc.description.abstractBackground: Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain ∼70 subunits that assemble on centromeric DNA in a hierarchical manner. Developing an accurate picture of the DNA-binding, linker and microtubule-binding layers of kinetochores, including the functions of individual proteins in these layers, is a key challenge in the field of yeast chromosome segregation. Moreover, comparison of orthologous proteins in yeast and humans promises to extend insight obtained from the study of simple fungal kinetochores to complex animal cell kinetochores. Principal Findings: We show that S. cerevisiae Spc105p forms a heterotrimeric complex with Kre28p, the likely orthologue of the metazoan kinetochore protein Zwint-1. Through systematic analysis of interdependencies among kinetochore complexes, focused on Spc105p/Kre28p, we develop a comprehensive picture of the assembly hierarchy of budding yeast kinetochores. We find Spc105p/Kre28p to comprise the third linker complex that, along with the Ndc80 and MIND linker complexes, is responsible for bridging between centromeric heterochromatin and kinetochore MAPs and motors. Like the Ndc80 complex, Spc105p/Kre28p is also essential for kinetochore binding by components of the spindle assembly checkpoint. Moreover, these functions are conserved in human cells. Conclusions/Significance: Spc105p/Kre28p is the last of the core linker complexes to be analyzed in yeast and we show it to be required for kinetochore binding by a discrete subset of kMAPs (Bim1p, Bik1p, Slk19p) and motors (Cin8p, Kar3p), all of which are nonessential. Strikingly, dissociation of these proteins from kinetochores prevents bipolar attachment, even though the Ndc80 and DASH complexes, the two best-studied kMAPs, are still present. The failure of Spc105 deficient kinetochores to bind correctly to spindle microtubules and to recruit checkpoint proteins in yeast and human cells explains the observed severity of missegregation phenotypes.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi://10.1371/journal.pone.0007640en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2764089/pdf/en_US
dash.licenseLAA
dc.subjectbiochemistryen_US
dc.subjectmacromolecular assemblies and machinesen_US
dc.subjectcell biologyen_US
dc.subjectcell growth and divisionen_US
dc.subjectgenetics and genomicsen_US
dc.subjectchromosome biologyen_US
dc.subjectmolecular biologyen_US
dc.subjectcentromeresen_US
dc.titleRoles for the Conserved Spc105p/Kre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpointen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorSorger, Peter Karl
dc.date.available2011-02-18T16:19:35Z
dash.affiliation.otherHMS^Systems Biologyen_US
dc.identifier.doi10.1371/journal.pone.0007640*
dash.contributor.affiliatedSorger, Peter


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