PMID:15371340

Citation	Cheeseman, IM, Niessen, S, Anderson, S, Hyndman, F, Yates, JR 3rd, Oegema, K and Desai, A (2004) A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. Genes Dev. 18:2255-68
Abstract	Kinetochores play an essential role in chromosome segregation by forming dynamic connections with spindle microtubules. Here, we identify a set of 10 copurifying kinetochore proteins from Caenorhabditis elegans, seven of which were previously uncharacterized. Using in vivo assays to monitor chromosome segregation, kinetochore assembly, and the mechanical stability of chromosome-microtubule attachments, we show that this copurifying protein network plays a central role at the kinetochore-microtubule interface. In addition, our analysis suggests that the network is comprised of three groups of proteins that contribute in distinct ways to this interface: KNL proteins act after the assembly of centromeric chromatin to generate the core of the microtubule-binding interface, MIS proteins control the rate and extent of formation of this interface, and NDC proteins are necessary to sustain tension during interactions with spindle microtubules. We also purify a similar set of associated proteins from human cells that includes four novel proteins and has recognizable homologs from each functional class. Thus, this protein network is a conserved constituent of the outer kinetochore, and the functions defined by our analysis in C. elegans are likely to be widely relevant.
Links	PubMed PMC517519 Online version:10.1101/gad.1234104
Keywords	Amino Acid Sequence; Animals; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Cycle Proteins; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Chromosome Segregation; Conserved Sequence; Embryo, Nonmammalian; HeLa Cells; Humans; Kinetochores/metabolism; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Mitosis; Mitotic Spindle Apparatus/physiology; Mutation; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phenotype; Protein Interaction Mapping/methods; Recombinant Proteins/genetics; Recombinant Proteins/isolation & purification; Recombinant Proteins/metabolism; Signal Transduction
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