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Orchestrating the Specific Assembly of Centromeric Nucleosomes

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Centromeres and Kinetochores

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 56))

Abstract

Centromeres are chromosomal loci that are defined epigenetically in most eukaryotes by incorporation of a centromere-specific nucleosome in which the canonical histone H3 variant is replaced by Centromere Protein A (CENP-A). Therefore, the assembly and propagation of centromeric nucleosomes are critical for maintaining centromere identify and ensuring genomic stability. Centromeres direct chromosome segregation (during mitosis and meiosis) by recruiting the constitutive centromere-associated network of proteins throughout the cell cycle that in turn recruits the kinetochore during mitosis. Assembly of centromere-specific nucleosomes in humans requires the dedicated CENP-A chaperone HJURP, and the Mis18 complex to couple the deposition of new CENP-A to the site of the pre-existing centromere, which is essential for maintaining centromere identity. Human CENP-A deposition occurs specifically in early G1, into pre-existing chromatin, and several additional chromatin-associated complexes regulate CENP-A nucleosome deposition and stability. Here we review the current knowledge on how new CENP-A nucleosomes are assembled selectively at the existing centromere in different species and how this process is controlled to ensure stable epigenetic inheritance of the centromere.

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  1. Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA

    Ewelina ZasadziƄska & Daniel R. Foltz

  2. Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Daniel R. Foltz

  3. Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA

    Daniel R. Foltz

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  1. Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Ben E. Black

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ZasadziƄska, E., Foltz, D.R. (2017). Orchestrating the Specific Assembly of Centromeric Nucleosomes. In: Black, B. (eds) Centromeres and Kinetochores. Progress in Molecular and Subcellular Biology, vol 56. Springer, Cham. https://doi.org/10.1007/978-3-319-58592-5_7

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