A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.

A defining feature of centromeres is the presence of the histone H3 variant CENP-A(Cnp1). It is not known how CENP-A(Cnp1) is specifically delivered to, and assembled into, centromeric chromatin. Through a screen for factors involved in kinetochore integrity in fission yeast, we identified Sim3. Sim3 is homologous to known histone ...
binding proteins NASP(Human) and N1/N2(Xenopus) and aligns with Hif1(S. cerevisiae), defining the SHNi-TPR family. Sim3 is distributed throughout the nucleoplasm, yet it associates with CENP-A(Cnp1) and also binds H3. Cells defective in Sim3 function have reduced levels of CENP-A(Cnp1) at centromeres (and increased H3) and display chromosome segregation defects. Sim3 is required to allow newly synthesized CENP-A(Cnp1) to accumulate at centromeres in S and G2 phase-arrested cells in a replication-independent mechanism. We propose that one function of Sim3 is to act as an escort that hands off CENP-A(Cnp1) to chromatin assembly factors, allowing its incorporation into centromeric chromatin.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Autoantigens, Binding Sites, Blotting, Western, Centromere, Chromatin Immunoprecipitation, Chromosomal Proteins, Non-Histone, Fungal Proteins, Green Fluorescent Proteins, Humans, Microscopy, Fluorescence, Molecular Sequence Data, Mutation, Nuclear Proteins, Protein Binding, Protein Structure, Tertiary, Protein Transport, Recombinant Fusion Proteins, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Sequence Homology, Amino Acid, Xenopus
Mol. Cell
Date: Dec. 28, 2007
Download Curated Data For This Publication
77266
Switch View:
  • Interactions 16