CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly

Viviana Barra, Yael Nechemia-Arbely, Don W. Cleveland, Peter Ly, Viviana Barra, Moira A. Mcmahon, Solène Hervé, Sebastian Hoffmann, Marie Dumont, Daniele Fachinetti

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Abstract

Human centromeres are defined by chromatin containing the histone H3 variant CENP-A assembled onto repetitive alphoid DNA sequences. By inducing rapid, complete degradation of endogenous CENP-A, we now demonstrate that once the first steps of centromere assembly have been completed in G1/S, continued CENP-A binding is not required for maintaining kinetochore attachment to centromeres or for centromere function in the next mitosis. Degradation of CENP-A prior to kinetochore assembly is found to block deposition of CENP-C and CENP-N, but not CENP-T, thereby producing defective kinetochores and failure of chromosome segregation. Without the continuing presence of CENP-A, CENP-B binding to alphoid DNA sequences becomes essential to preserve anchoring of CENP-C and the kinetochore to each centromere. Thus, there is a reciprocal interdependency of CENP-A chromatin and the underlying repetitive centromere DNA sequences bound by CENP-B in the maintenance of human chromosome segregation.
Lingua originaleEnglish
pagine (da-a)2394-2404
Numero di pagine11
RivistaCell Reports
Volume17
Stato di pubblicazionePublished - 2016

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All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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Barra, V., Nechemia-Arbely, Y., Cleveland, D. W., Ly, P., Barra, V., Mcmahon, M. A., Hervé, S., Hoffmann, S., Dumont, M., & Fachinetti, D. (2016). CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly. Cell Reports, 17, 2394-2404.