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

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

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2394-2404
Number of pages11
JournalCell Reports
Volume17
Issue number9
DOIs
StatePublished - Nov 22 2016

Keywords

  • CENP-A
  • CENP-B
  • CENP-C
  • auxin
  • centromere
  • chromosome segregation
  • epigenetic
  • kinetochore
  • mitosis
  • protein degradation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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