Priming of Centromere for CENP-A Recruitment by Human hMis18α, hMis18β, and M18BP1

• DOI: 10.1016/j.devcel.2006.11.002
• Publication Date: 2007-02-03T07:53:21Z
• Authors: Yohta Fujita; Takeshi Hayashi; Tomomi Kiyomitsu; Yusuke Toyoda; Aya Kokubu; Chikashi Obuse; Mitsuhiro Yanagida
• Keywords: 0301 basic medicine; Chromosomal Proteins, Non-Histone; Amino Acid Motifs; Centromere; Molecular Sequence Data; Cell Cycle Proteins; CELLCYCLE; Hydroxamic Acids; Autoantigens; 03 medical and health sciences; Chromosome Segregation; Consensus Sequence; Animals; Humans; Amino Acid Sequence; Metaphase; Phylogeny; Adaptor Proteins, Signal Transducing; Genome, Human; Mutation; CELLBIO; Centromere Protein A; Developmental Biology; HeLa Cells; Protein Binding

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.