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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays

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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
Journal Article

Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays

2026
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Overview
Human kinetochores assemble onto centromeric DNA comprising repetitive arrays of the 171 bp α-satellite sequence. To understand the higher-order architecture of the inner kinetochore assembled onto α-satellite arrays, we show cryo-EM structures of CCAN with free DNA, and α-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 α-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 α-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 α-satellite chromatin containing CENP-A nucleosomes. Based on cryo-EM structures, here the authors propose three models for how the inner kinetochore and CENP-A nucleosomes are organized on repetitive alpha-satellite sequences, providing insights into the higher-order architecture of human centromeres.