| First Author | Roulland Y | Year | 2016 |
| Journal | Mol Cell | Volume | 63 |
| Issue | 4 | Pages | 674-685 |
| PubMed ID | 27499292 | Mgi Jnum | J:249126 |
| Mgi Id | MGI:6093934 | Doi | 10.1016/j.molcel.2016.06.023 |
| Citation | Roulland Y, et al. (2016) The Flexible Ends of CENP-A Nucleosome Are Required for Mitotic Fidelity. Mol Cell 63(4):674-685 |
| abstractText | 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 alphaN-helix of CENP-A with the 3-turn alphaN-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. |
