Kinetochore Components Required for Centromeric Chromatin Assembly Are Impacted by Msc1 in  Schizosaccharomyces pombe .
Eukaryotic chromosome segregation requires a protein complex known as the kinetochore that mediates attachment between mitotic spindle microtubules and centromere-specific nucleosomes composed of the widely conserved histone variant CENP-A. Mutations in kinetochore proteins of the fission yeast  Schizosaccharomyces pombe  lead to chromosome missegregation such that daughter cells emerge from mitosis with unequal DNA content. We find that multiple copies of Msc1-a fission yeast homolog of the KDM5 family of proteins-suppresses the temperature-sensitive growth defect of several kinetochore mutants, including  mis16  and  mis18 , as well as  mis6 ,  mis15 , and  mis17 , components of the Constitutive Centromere Associated Network (CCAN). On the other hand, deletion of  msc1  exacerbates both the growth defect and chromosome missegregation phenotype of each of these mutants. The C-terminal PHD domains of Msc1, previously shown to associate with a histone deacetylase activity, are necessary for Msc1 function when kinetochore mutants are compromised. We also demonstrate that, in the absence of Msc1, the frequency of localization to the kinetochore of Mis16 and Mis15 is altered from wild-type cells. As we show here for  msc1 , others have shown that elevating  cnp1  levels acts similarly to promote survival of the CCAN mutants. The rescue of  mis15  and  mis17  by  cnp1  is, however, independent of  msc1  Thus, Msc1 appears to contribute to the chromatin environment at the centromere: the absence of Msc1 sensitizes cells to perturbations in kinetochore function, while elevating Msc1 overcomes loss of function of critical components of the kinetochore and centromere.
Gao C, Langbein L, Kamal F, George AA, Walworth NC