TY - JOUR
T1 - The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity
AU - Roulland, Yohan
AU - Ouararhni, Khalid
AU - Naidenov, Mladen
AU - Ramos, Lorrie
AU - Shuaib, Muhammad
AU - Syed, Sajad Hussain
AU - Lone, Imtiaz Nizar
AU - Boopathi, Ramachandran
AU - Fontaine, Emeline
AU - Papai, Gabor
AU - Tachiwana, Hiroaki
AU - Gautier, Thierry
AU - Skoufias, Dimitrios
AU - Padmanabhan, Kiran
AU - Bednar, Jan
AU - Kurumizaka, Hitoshi
AU - Schultz, Patrick
AU - Angelov, Dimitar
AU - Hamiche, Ali
AU - Dimitrov, Stefan
PY - 2016/8/18
Y1 - 2016/8/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.molcel.2016.06.023
DO - 10.1016/j.molcel.2016.06.023
M3 - Article
C2 - 27499292
AN - SCOPUS:84992697331
SN - 1097-2765
VL - 63
SP - 674
EP - 685
JO - Molecular Cell
JF - Molecular Cell
IS - 4
ER -