The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity

Yohan Roulland; Khalid Ouararhni; Mladen Naidenov; Lorrie Ramos; Muhammad Shuaib; Sajad Hussain Syed; Imtiaz Nizar Lone; Ramachandran Boopathi; Emeline Fontaine; Gabor Papai; Hiroaki Tachiwana; Thierry Gautier; Dimitrios Skoufias; Kiran Padmanabhan; Jan Bednar; Hitoshi Kurumizaka; Patrick Schultz; Dimitar Angelov; Ali Hamiche; Stefan Dimitrov

doi:10.1016/j.molcel.2016.06.023

The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity

Yohan Roulland
, Khalid Ouararhni
, Mladen Naidenov
, Lorrie Ramos
, Muhammad Shuaib
, Sajad Hussain Syed
, Imtiaz Nizar Lone
, Ramachandran Boopathi
, Emeline Fontaine
, Gabor Papai
, Hiroaki Tachiwana
, Thierry Gautier
, Dimitrios Skoufias
, Kiran Padmanabhan
, Jan Bednar
, Hitoshi Kurumizaka
, Patrick Schultz
, Dimitar Angelov^*
, Ali Hamiche
, Stefan Dimitrov

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

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.

Original language	English
Pages (from-to)	674-685
Number of pages	12
Journal	Molecular Cell
Volume	63
Issue number	4
DOIs	https://doi.org/10.1016/j.molcel.2016.06.023
Publication status	Published - 18 Aug 2016
Externally published	Yes

Access to Document

10.1016/j.molcel.2016.06.023

Cite this

Roulland, Y., Ouararhni, K., Naidenov, M., Ramos, L., Shuaib, M., Syed, S. H., Lone, I. N., 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. (2016). The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity. Molecular Cell, 63(4), 674-685. https://doi.org/10.1016/j.molcel.2016.06.023

@article{e82e8ab3784046b5b62c5b4be40ca595,

title = "The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity",

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.",

author = "Yohan Roulland and Khalid Ouararhni and Mladen Naidenov and Lorrie Ramos and Muhammad Shuaib and Syed, \{Sajad Hussain\} and Lone, \{Imtiaz Nizar\} and Ramachandran Boopathi and Emeline Fontaine and Gabor Papai and Hiroaki Tachiwana and Thierry Gautier and Dimitrios Skoufias and Kiran Padmanabhan and Jan Bednar and Hitoshi Kurumizaka and Patrick Schultz and Dimitar Angelov and Ali Hamiche and Stefan Dimitrov",

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = aug,

day = "18",

doi = "10.1016/j.molcel.2016.06.023",

language = "English",

volume = "63",

pages = "674--685",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "4",

}

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 2016, 'The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity', Molecular Cell, vol. 63, no. 4, pp. 674-685. https://doi.org/10.1016/j.molcel.2016.06.023

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.

UR - https://www.scopus.com/pages/publications/84992697331

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 -

The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity

Abstract

Access to Document

Other files and links

Fingerprint

Cite this