title: CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly.
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.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Dumont
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France.
authors.forename: Viviana
authors.initials: V
authors.lastname: Barra
authors.affiliation: 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.
authors.forename: Peter
authors.initials: P
authors.lastname: Ly
authors.affiliation: 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.
authors.forename: Yael
authors.initials: Y
authors.lastname: Nechemia-Arbely
authors.affiliation: 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.
authors.forename: Moira A
authors.initials: MA
authors.lastname: McMahon
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Hervé
authors.affiliation: 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.
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, 26 rue d'Ulm, F-75005, Paris, France. Electronic address: daniele.fachinetti@curie.fr.
authors.forename: Daniele
authors.initials: D
authors.lastname: Fachinetti
mesh_terms: D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism*; D000076247:Centromere Protein A / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D044127:Epigenesis, Genetic; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis; D008954:Models, Biological
chemical_list: D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone
keywords: CENP-A; CENP-B; CENP-C; auxin; centromere; chromosome segregation; epigenetic; kinetochore; mitosis; protein degradation