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

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

Author information

1
Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France.
2
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
3
Ludwig Institute for Cancer Research, University of California at San Diego, La Jolla, CA 92093, USA; Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: dcleveland@ucsd.edu.
4
Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France. Electronic address: daniele.fachinetti@curie.fr.

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.

KEYWORDS:

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

PMID:
27880912
PMCID:
PMC5134894
DOI:
10.1016/j.celrep.2016.10.084
[Indexed for MEDLINE]
Free PMC Article

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