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

The centromere is crucial for the proper segregation of chromosomes in all eukaryotic cells. We identified a centromeric protein, Nuf2, which is conse rved 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 elo ngated without segregating the chromosomes, indicating that spindle functio n was compromised, but that this abnormality did not result in metaphase ar rest. Certain nuf2 temperature-sensitive mutations, however, caused metapha se 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 de pendent on the spindle checkpoint component Mad2. Interestingly, Nuf2 disap peared from the centromere during meiotic prophase when centromeres lose th eir connection to the spindle pole body. We propose that Nuf2 acts at the c entromere to establish a connection with the spindle for proper chromosome segregation, and that Nuf2 function is also required for the spindle checkp oint.