RRC ID 12593
Author Dunleavy EM, Pidoux AL, Monet M, Bonilla C, Richardson W, Hamilton GL, Ekwall K, McLaughlin PJ, Allshire RC.
Title A NASP (N1/N2)-related protein, Sim3, binds CENP-A and is required for its deposition at fission yeast centromeres.
Journal Mol. Cell
Abstract 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.
Volume 28(6)
Pages 1029-44
Published 2007-12-28
DOI 10.1016/j.molcel.2007.10.010
PII S1097-2765(07)00692-2
PMID 18158900
PMC PMC2193228
MeSH Amino Acid Motifs Amino Acid Sequence Animals Autoantigens / genetics Autoantigens / metabolism* Binding Sites Blotting, Western Centromere / metabolism* Centromere Protein A Chromatin Immunoprecipitation Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism* Fungal Proteins / genetics Fungal Proteins / metabolism* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Microscopy, Fluorescence Molecular Sequence Data Mutation Nuclear Proteins / genetics Nuclear Proteins / metabolism* Protein Binding Protein Structure, Tertiary Protein Transport Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Schizosaccharomyces / chemistry Schizosaccharomyces / genetics Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / genetics Schizosaccharomyces pombe Proteins / metabolism* Sequence Homology, Amino Acid Xenopus
IF 14.248
Times Cited 62
Yeast FY8481