Fiche publication
Date publication
août 2016
Journal
Molecular cell
Auteurs
Membres identifiés du Cancéropôle Est :
Dr HAMICHE Ali
,
Dr SCHULTZ Patrick
Tous les auteurs :
Roulland Y, Ouararhni K, Naidenov M, Ramos L, Shuaib M, Syed SH, Lone IN, Boopathi R, Fontaine E, Papai G, Tachiwana H, Gautier T, Skoufias D, Padmanabhan K, Bednar J, Kurumizaka H, Schultz P, Angelov D, Hamiche A, Dimitrov S
Lien Pubmed
Résumé
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 αN-helix of CENP-A with the 3-turn αN-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.
Référence
Mol. Cell. 2016 Aug;63(4):674-85
