title: A conserved protein, Nuf2, is implicated in connecting the centromere to the spindle during chromosome segregation: a link between the kinetochore function and the spindle checkpoint.
abstract: The centromere is crucial for the proper segregation of chromosomes in all eukaryotic cells. We identified a centromeric protein, Nuf2, which is conserved in fission yeast, human, nematode, and budding yeast. Gene disruption of nuf2+ in the fission yeast Schizosaccharomyces pombe caused defects in chromosome segregation and the spindle checkpoint: the mitotic spindle elongated without segregating the chromosomes, indicating that spindle function was compromised, but that this abnormality did not result in metaphase arrest. Certain nuf2 temperature-sensitive mutations, however, caused metaphase arrest with condensed chromosomes and a short spindle, indicating that, while these mutations caused abnormalities in spindle function, the spindle checkpoint pathway remained intact. Metaphase arrest in these cells was dependent on the spindle checkpoint component Mad2. Interestingly, Nuf2 disappeared from the centromere during meiotic prophase when centromeres lose their connection to the spindle pole body. We propose that Nuf2 acts at the centromere to establish a connection with the spindle for proper chromosome segregation, and that Nuf2 function is also required for the spindle checkpoint.
authors.affiliation: Cell Biology Group, Kansai Advanced Research Center, Communications Research Laboratory, Kobe, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Nabetani
authors.forename: T
authors.initials: T
authors.lastname: Koujin
authors.forename: C
authors.initials: C
authors.lastname: Tsutsumi
authors.forename: T
authors.initials: T
authors.lastname: Haraguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraoka
mesh_terms: D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins; D002503:Centromere / Q000502:physiology*; D020090:Chromosome Segregation / Q000502:physiology*; D015825:Chromosomes, Fungal; D017124:Conserved Sequence; D005656:Fungal Proteins / Q000502:physiology*; D018816:Genes, cdc / Q000502:physiology*; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000502:physiology*; D008164:Luminescent Proteins; D008540:Meiosis; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000502:physiology*; D021101:Radiation Hybrid Mapping; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D008941:Spindle Apparatus / Q000502:physiology*; D013696:Temperature
chemical_list: D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D008164:Luminescent Proteins; C087340:NUF2 protein, S cerevisiae; C490197:NUF2 protein, human; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C490196:nuf2 protein, S pombe; D049452:Green Fluorescent Proteins