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.
Hoffmann S., Dumont M., Barra V., Ly P., Nechemia-Arbely Y., McMahon M.A., et al. (2016). CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly. CELL REPORTS, 17(9), 2394-2404.
Data di pubblicazione: | 2016 |
Titolo: | CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly |
Autori: | |
Citazione: | Hoffmann S., Dumont M., Barra V., Ly P., Nechemia-Arbely Y., McMahon M.A., et al. (2016). CENP-A Is Dispensable for Mitotic Centromere Function after Initial Centromere/Kinetochore Assembly. CELL REPORTS, 17(9), 2394-2404. |
Rivista: | |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.celrep.2016.10.084 |
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. |
Settore Scientifico Disciplinare: | Settore BIO/18 - Genetica |
Appare nelle tipologie: | 1.01 Articolo in rivista |
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