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

• DOI: 10.1126/science.abn3810
• Publication Date: 2022-04-14T17:59:05Z
• Authors: Stanislau Yatskevich; Kyle W. Muir; Dom Bellini; Ziguo Zhang; Jing Yang; Thomas Tischer; Masa Predin; Tom Dendooven; Stephen H. McLaug...; David Barford
• Keywords: 0301 basic medicine; 03 medical and health sciences; Centromere; Cryoelectron Microscopy; Humans; DNA; Kinetochores; Centromere Protein A; Nucleosomes; Protein Binding

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