@article{ac7bc40b1cb44bdd9f3723b1c1216662,
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.",
keywords = "CENP-A, CENP-B, CENP-C, auxin, centromere, chromosome segregation, epigenetic, kinetochore, mitosis, protein degradation",
author = "Sebastian Hoffmann and Marie Dumont and Viviana Barra and Peter Ly and Yael Nechemia-Arbely and McMahon, {Moira A.} and Sol{\`e}ne Herv{\'e} and Cleveland, {Don W.} and Daniele Fachinetti",
note = "Funding Information: The authors would like to thank B.E. Black (University of Pennsylvania, Philadelphia), C. Bartocci (Institut Curie, Paris), Dong Hyun Kim (Ludwig Institute for Cancer Research, La Jolla), Amira Abdullah (Ludwig Institute for Cancer Research), and Vincent Fraisier (Institut Curie) for helpful suggestions and technical help, and K. McKinley and I. Cheeseman (MIT, Boston), A. Desai (Ludwig Institute for Cancer Research), G. Orsi and G. Almouzni (Institut Curie), I. Draskovic and A. Londono (Institut Curie), Song-Tao Liu (University of Toledo), A. Miyawaki (Hirosawa), and B.E. Black (University of Pennsylvania) for providing reagents. We also thank the FACS facility in the Sanford Consortium for Regenerative Medicine (La Jolla) and the PICT imaging platform at Institut Curie , part of the national infrastructure France-BioImaging (grant ANR-10-INSB-04 ). D.W.C. has received support from NIH grant R01 GM074150 . D.W.C. receives salary support from the Ludwig Institute for Cancer Research . D.F. receives salary support from the CNRS . D.F. has received support by Labex “CelTisPhyBio,” the Institut Curie , and the ATIP-Avenir 2015 program . This work has also received support under the program “Investissements d{\textquoteright}Avenir,” launched by the French Government and implemented by ANR with the references ANR-10-LABX-0038 and ANR-10-IDEX-0001-02 PSL . Publisher Copyright: {\textcopyright} 2016 The Author(s)",
year = "2016",
month = nov,
day = "22",
doi = "10.1016/j.celrep.2016.10.084",
language = "English (US)",
volume = "17",
pages = "2394--2404",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}