| Literature DB >> 27499292 |
Yohan Roulland1, Khalid Ouararhni2, Mladen Naidenov3, Lorrie Ramos1, Muhammad Shuaib2, Sajad Hussain Syed4, Imtiaz Nizar Lone4, Ramachandran Boopathi4, Emeline Fontaine1, Gabor Papai5, Hiroaki Tachiwana6, Thierry Gautier1, Dimitrios Skoufias7, Kiran Padmanabhan8, Jan Bednar1, Hitoshi Kurumizaka6, Patrick Schultz5, Dimitar Angelov9, Ali Hamiche10, Stefan Dimitrov11.
Abstract
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.Entities:
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Year: 2016 PMID： 27499292 DOI： 10.1016/j.molcel.2016.06.023
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970