Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Autoantigens / metabolism*
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Cell Cycle Proteins
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Centromere / drug effects
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Centromere / metabolism*
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Centromere Protein A
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Chromosomal Proteins, Non-Histone / chemistry
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Chromosomal Proteins, Non-Histone / metabolism*
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Chromosome Segregation / drug effects
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Consensus Sequence
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Genome, Human / drug effects
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HeLa Cells
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Humans
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Hydroxamic Acids / pharmacology
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Metaphase / drug effects
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Molecular Sequence Data
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Mutation / genetics
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Phylogeny
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Protein Binding / drug effects
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Protein Transport / drug effects
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Proto-Oncogene Proteins c-myb / metabolism
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RNA Interference
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Recombinant Fusion Proteins / metabolism
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Schizosaccharomyces pombe Proteins / metabolism
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Telophase / drug effects
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Vertebrates
Substances
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Adaptor Proteins, Signal Transducing
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Autoantigens
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CENPA protein, human
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Cell Cycle Proteins
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Centromere Protein A
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Chromosomal Proteins, Non-Histone
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Hydroxamic Acids
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MIS18A protein, human
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MIS18BP1 protein, human
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OIP5 protein, human
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Proto-Oncogene Proteins c-myb
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Recombinant Fusion Proteins
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Schizosaccharomyces pombe Proteins
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trichostatin A