The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity

Yohan Roulland, Khalid Ouararhni, Mladen Naidenov, Lorrie Ramos, Muhammad Shuaib, Sajad Hussain Syed, Imtiaz Nizar Lone, Ramachandran Boopathi, Emeline Fontaine, Gabor Papai, Hiroaki Tachiwana, Thierry Gautier, Dimitrios Skoufias, Kiran Padmanabhan, Jan Bednar, Hitoshi Kurumizaka, Patrick Schultz, Dimitar Angelov, Ali Hamiche, Stefan Dimitrov

    Research output: Contribution to journalArticle

    27 Citations (Scopus)

    Abstract

    CENP-A is a histone variant, which replaces histone H3 at centromeres and confers unique properties to centromeric chromatin. The crystal structure of CENP-A nucleosome suggests flexible nucleosomal DNA ends, but their dynamics in solution remains elusive and their implication in centromere function is unknown. Using electron cryo-microscopy, we determined the dynamic solution properties of the CENP-A nucleosome. Our biochemical, proteomic, and genetic data reveal that higher flexibility of DNA ends impairs histone H1 binding to the CENP-A nucleosome. Substituting the 2-turn αN-helix of CENP-A with the 3-turn αN-helix of H3 results in compact particles with rigidified DNA ends, able to bind histone H1. In vivo replacement of CENP-A with H3-CENP-A hybrid nucleosomes leads to H1 recruitment, delocalization of kinetochore proteins, and significant mitotic and cytokinesis defects. Our data reveal that the evolutionarily conserved flexible ends of the CENP-A nucleosomes are essential to ensure the fidelity of the mitotic pathway.

    Original languageEnglish
    Pages (from-to)674-685
    Number of pages12
    JournalMolecular Cell
    Volume63
    Issue number4
    DOIs
    Publication statusPublished - 2016 Aug 18

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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  • Cite this

    Roulland, Y., Ouararhni, K., Naidenov, M., Ramos, L., Shuaib, M., Syed, S. H., Lone, I. N., Boopathi, R., Fontaine, E., Papai, G., Tachiwana, H., Gautier, T., Skoufias, D., Padmanabhan, K., Bednar, J., Kurumizaka, H., Schultz, P., Angelov, D., Hamiche, A., & Dimitrov, S. (2016). The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity. Molecular Cell, 63(4), 674-685. https://doi.org/10.1016/j.molcel.2016.06.023