Priming of centromere for CENP-A recruitment by human hMis18alpha, hMis18beta, and M18BP1

Dev Cell. 2007 Jan;12(1):17-30. doi: 10.1016/j.devcel.2006.11.002.


The centromere is the chromosomal site that joins to microtubules during mitosis for proper segregation. Determining the location of a centromere-specific histone H3 called CENP-A at the centromere is vital for understanding centromere structure and function. Here, we report the identification of three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere. We provide evidence that such centromeric localization of hMis18 is essential for the subsequent recruitment of de novo-synthesized CENP-A. If any of the three is knocked down by RNAi, centromere recruitment of newly synthesized CENP-A is rapidly abolished, followed by defects such as misaligned chromosomes, anaphase missegregation, and interphase micronuclei. Tricostatin A, an inhibitor to histone deacetylase, suppresses the loss of CENP-A recruitment to centromeres in hMis18alpha RNAi cells. Telophase centromere chromatin may be primed or licensed by the hMis18 complex and RbAp46/48 to recruit CENP-A through regulating the acetylation status in the centromere.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Autoantigens / metabolism*
  • Cell Cycle Proteins
  • Centromere / drug effects
  • Centromere / metabolism*
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Chromosome Segregation / drug effects
  • Consensus Sequence
  • Genome, Human / drug effects
  • HeLa Cells
  • Humans
  • Hydroxamic Acids / pharmacology
  • Metaphase / drug effects
  • Molecular Sequence Data
  • Mutation / genetics
  • Phylogeny
  • Protein Binding / drug effects
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-myb / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism
  • Schizosaccharomyces pombe Proteins / metabolism
  • Telophase / drug effects
  • Vertebrates


  • Adaptor Proteins, Signal Transducing
  • Autoantigens
  • CENPA protein, human
  • Cell Cycle Proteins
  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone
  • Hydroxamic Acids
  • MIS18A protein, human
  • MIS18BP1 protein, human
  • OIP5 protein, human
  • Proto-Oncogene Proteins c-myb
  • Recombinant Fusion Proteins
  • Schizosaccharomyces pombe Proteins
  • trichostatin A