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

Cell Rep. 2016 Nov 22;17(9):2394-2404. doi: 10.1016/j.celrep.2016.10.084.


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.

Keywords: CENP-A; CENP-B; CENP-C; auxin; centromere; chromosome segregation; epigenetic; kinetochore; mitosis; protein degradation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Centromere / metabolism*
  • Centromere Protein A / metabolism*
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation
  • Epigenesis, Genetic
  • Humans
  • Kinetochores / metabolism*
  • Mitosis*
  • Models, Biological


  • Centromere Protein A
  • Chromosomal Proteins, Non-Histone