期刊
MOLECULAR CELL
卷 63, 期 4, 页码 674-685出版社
CELL PRESS
DOI: 10.1016/j.molcel.2016.06.023
关键词
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资金
- Universite de Strasbourg (UDS)
- Universite de Grenoble Alpes (UGA)
- Centre National de la Recherche Scientifique (CNRS)
- Institut National de la Sante et de la Recherche Medicale (INSERM) (Plan Cancer)
- Institut National du Cancer (INCA) [INCa_4496, INCa_4454, INCa PLBIO15-245]
- Agence Nationale de la Recherche (ANR) (VariZome)
- Agence Nationale de la Recherche (ANR) (CHROMCOMP)
- Agence Nationale de la Recherche (ANR) (CHROME)
- Agence Nationale de la Recherche (ANR) (CENP-A)
- Fondation pour la Recherche Medicale (FRM) [DEP20131128521]
- Universite de Strasbourg Institut d'Etudes Avancees [USIAS-2015-42]
- Association pour la Recherche sur le Cancer
- La Ligue Nationale contre le Cancer (Equipe labellisee)
- Equipex Equip@Meso project
- Labex INRT
- La Ligue Nationale contre le Cancer
- ATIP-AVENIR starting grant
- JSPS [JP25116002]
- Grants-in-Aid for Scientific Research [25116002] Funding Source: KAKEN
CENP-A is a histone variant, which replaces histone H3 at centromeres and confers unique properties to centromeric chromatin. The crystal structure of CENP-A nucleosome suggests flexible nucleosomal DNA ends, but their dynamics in solution remains elusive and their implication in centromere function is unknown. Using electron cryo-microscopy, we determined the dynamic solution properties of the CENP-A nucleosome. Our biochemical, proteomic, and genetic data reveal that higher flexibility of DNA ends impairs histone H1 binding to the CENP-A nucleosome. Substituting the 2-turn alpha N-helix of CENP-A with the 3-turn alpha N-helix of H3 results in compact particles with rigidified DNA ends, able to bind histone H1. In vivo replacement of CENP-A with H3-CENP-A hybrid nucleosomes leads to H1 recruitment, delocalization of kinetochore proteins, and significant mitotic and cytokinesis defects. Our data reveal that the evolutionarily conserved flexible ends of the CENP-A nucleosomes are essential to ensure the fidelity of the mitotic pathway.
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