PMID:14522947

Citation	Desai, A, Rybina, S, Müller-Reichert, T, Shevchenko, A, Shevchenko, A, Hyman, A and Oegema, K (2003) KNL-1 directs assembly of the microtubule-binding interface of the kinetochore in C. elegans. Genes Dev. 17:2421-35
Abstract	Segregation of the replicated genome during cell division requires kinetochores, mechanochemical organelles that assemble on mitotic chromosomes to connect them to spindle microtubules. CENP-A, a histone H3 variant, and CENP-C, a conserved structural protein, form the DNA-proximal foundation for kinetochore assembly. Using RNA interference-based genomics in Caenorhabditis elegans, we identified KNL-1, a novel kinetochore protein whose depletion, like that of CeCENP-A or CeCENP-C, leads to a "kinetochore-null" phenotype. KNL-1 is downstream of CeCENP-A and CeCENP-C in a linear assembly hierarchy. In embryonic extracts, KNL-1 exhibits substoichiometric interactions with CeCENP-C and forms a near-stoichiometric complex with CeNDC-80 and HIM-10, the C. elegans homologs of Ndc80p/HEC1p and Nuf2p-two widely conserved outer kinetochore components. However, CeNDC-80 and HIM-10 are not functionally equivalent to KNL-1 because their inhibition, although preventing formation of a mechanically stable kinetochore-microtubule interface and causing chromosome missegregation, does not result in a kinetochore-null phenotype. The greater functional importance of KNL-1 may be due to its requirement for targeting multiple components of the outer kinetochore, including CeNDC-80 and HIM-10. Thus, KNL-1 plays a central role in translating the initiation of kinetochore assembly by CeCENP-A and CeCENP-C into the formation of a functional microtubule-binding interface.
Links	PubMed PMC218079 Online version:10.1101/gad.1126303
Keywords	Amino Acid Sequence; Animals; Autoantigens; Binding Sites; Caenorhabditis elegans/cytology; Caenorhabditis elegans/embryology; Caenorhabditis elegans/physiology; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Centromere Protein B; Chromosomal Proteins, Non-Histone/genetics; Chromosomal Proteins, Non-Histone/metabolism; Chromosome Segregation; DNA-Binding Proteins; Embryo, Nonmammalian; Fungal Proteins/genetics; Fungal Proteins/metabolism; Kinetochores/metabolism; Microtubule-Associated Proteins/genetics; Microtubule-Associated Proteins/metabolism; Microtubules/metabolism; Mitosis; Molecular Sequence Data; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; RNA Interference; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid
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