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Structure of the human inner kinetochore bound to a centromeric CENP-A nucleosome

DOI: 10.1126/science.abn3810 DOI Help

Authors: Stanislau Yatskevich (MRC Laboratory of Molecular Biology) , Kyle W. Muir (MRC Laboratory of Molecular Biology) , Dom Bellini (MRC Laboratory of Molecular Biology) , Ziguo Zhang (MRC Laboratory of Molecular Biology) , Jing Yang (MRC Laboratory of Molecular Biology) , Thomas Tischer (MRC Laboratory of Molecular Biology) , Masa Predin (MRC Laboratory of Molecular Biology) , Tom Dendooven (MRC Laboratory of Molecular Biology) , Stephen H. Mclaughlin (MRC Laboratory of Molecular Biology) , David Barford (MRC Laboratory of Molecular Biology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science

State: Published (Approved)
Published: April 2022

Abstract: Kinetochores assemble onto specialized centromeric CENP-A nucleosomes (CENP-ANuc) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-EM structures of the human inner kinetochore CCAN (Constitutive Centromere Associated Network) complex bound to CENP-ANuc reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-ANuc, while a linker DNA segment of the α-satellite repeat emerges from the fully-wrapped end of the nucleosome to thread through the central CENP-LN channel that tightly grips the DNA. The CENP-TWSX histone-fold module further augments DNA binding and partially wraps the linker DNA in a manner reminiscent of canonical nucleosomes. Our study suggests that the topological entrapment of the linker DNA by CCAN provides a robust mechanism by which kinetochores withstand both pushing and pulling forces exerted by the mitotic spindle.

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 21/04/2022 09:31

Discipline Tags:

Structural biology Life Sciences & Biotech

Technical Tags:

Microscopy Electron Microscopy (EM) Cryo Electron Microscopy (Cryo EM)