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Structure of the human inner kinetochore CCAN bound to a di-CENP-A nucleosome
Structural highlights
FunctionCENPH_HUMAN Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.[1] [2] [3] Publication Abstract from PubMedHuman kinetochores assemble onto centromeric DNA comprising repetitive arrays of the 171 bp alpha-satellite sequence. To understand the higher-order architecture of the inner kinetochore assembled onto alpha-satellite arrays, we show cryo-EM structures of CCAN with free DNA, and alpha-satellite repeat monomers and dimers with CENP-A nucleosomes. CCAN bound to free DNA and a monomeric CENP-A nucleosome engages 70 bp of DNA comprising 30 bp of an upstream alpha-satellite repeat. This upstream DNA interacts with the histone-fold domain subunits of the CENP-TWSX module in a manner resembling how nucleosomes wrap DNA gyres. A complex of CCAN assembled onto a dimeric alpha-satellite repeat with two CENP-A nucleosomes shows that CCAN can only be accommodated on the linker DNA by unwrapping DNA from both the CENP-TWSX module and the upstream nucleosome. We discuss the implications of these results for models of CCAN assembly on arrays of alpha-satellite chromatin containing CENP-A nucleosomes. Models for the architecture of the human inner kinetochore on centromeric alpha-satellite CENP-A nucleosome arrays.,Yu C, Muir KW, Yang J, Zhang Z, McLaughlin SH, Barford D Nat Commun. 2026 May 12. doi: 10.1038/s41467-026-72856-0. PMID:42120391[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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