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Yatskevich, Stanislau; Muir, Kyle W; Bellini, Dom; Zhang, Ziguo; Yang, Jing; Tischer, Thomas; Predin, Masa; Dendooven, Tom; McLaughlin, Stephen H; Barford, David
Science, 05/2022, Volume: 376, Issue: 6595Journal Article
Kinetochores assemble onto specialized centromeric CENP-A (centromere protein A) nucleosomes (CENP-A ) to mediate attachments between chromosomes and the mitotic spindle. We describe cryo-electron microscopy structures of the human inner kinetochore constitutive centromere associated network (CCAN) complex bound to CENP-A reconstituted onto α-satellite DNA. CCAN forms edge-on contacts with CENP-A , and 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.
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