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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
by
Muir, Kyle W.
, Yang, Jing
, McLaughlin, Stephen H.
, Yu, Cong
, Barford, David
, Zhang, Ziguo
in
101/28
/ 631/45/535/1258/1259
/ 631/80/103/1966
/ 631/80/103/90
/ 82/80
/ 82/83
/ Arrays
/ Centromere - metabolism
/ Centromere - ultrastructure
/ Centromere protein A
/ Centromere Protein A - chemistry
/ Centromere Protein A - genetics
/ Centromere Protein A - metabolism
/ Centromere Protein A - ultrastructure
/ Centromeres
/ Chromatin
/ Chromosomal Proteins, Non-Histone - metabolism
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ DNA - chemistry
/ DNA - metabolism
/ DNA, Satellite - chemistry
/ DNA, Satellite - genetics
/ DNA, Satellite - metabolism
/ Gyres
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Kinetochores
/ Kinetochores - chemistry
/ Kinetochores - metabolism
/ Kinetochores - ultrastructure
/ Models, Molecular
/ Modules
/ multidisciplinary
/ Nucleosomes
/ Nucleosomes - chemistry
/ Nucleosomes - metabolism
/ Nucleosomes - ultrastructure
/ Nucleotide sequence
/ Satellite DNA
/ Science
/ Science (multidisciplinary)
/ Sequences
2026
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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
by
Muir, Kyle W.
, Yang, Jing
, McLaughlin, Stephen H.
, Yu, Cong
, Barford, David
, Zhang, Ziguo
in
101/28
/ 631/45/535/1258/1259
/ 631/80/103/1966
/ 631/80/103/90
/ 82/80
/ 82/83
/ Arrays
/ Centromere - metabolism
/ Centromere - ultrastructure
/ Centromere protein A
/ Centromere Protein A - chemistry
/ Centromere Protein A - genetics
/ Centromere Protein A - metabolism
/ Centromere Protein A - ultrastructure
/ Centromeres
/ Chromatin
/ Chromosomal Proteins, Non-Histone - metabolism
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ DNA - chemistry
/ DNA - metabolism
/ DNA, Satellite - chemistry
/ DNA, Satellite - genetics
/ DNA, Satellite - metabolism
/ Gyres
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Kinetochores
/ Kinetochores - chemistry
/ Kinetochores - metabolism
/ Kinetochores - ultrastructure
/ Models, Molecular
/ Modules
/ multidisciplinary
/ Nucleosomes
/ Nucleosomes - chemistry
/ Nucleosomes - metabolism
/ Nucleosomes - ultrastructure
/ Nucleotide sequence
/ Satellite DNA
/ Science
/ Science (multidisciplinary)
/ Sequences
2026
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Models for the architecture of the human inner kinetochore on centromeric α-satellite CENP-A nucleosome arrays
by
Muir, Kyle W.
, Yang, Jing
, McLaughlin, Stephen H.
, Yu, Cong
, Barford, David
, Zhang, Ziguo
in
101/28
/ 631/45/535/1258/1259
/ 631/80/103/1966
/ 631/80/103/90
/ 82/80
/ 82/83
/ Arrays
/ Centromere - metabolism
/ Centromere - ultrastructure
/ Centromere protein A
/ Centromere Protein A - chemistry
/ Centromere Protein A - genetics
/ Centromere Protein A - metabolism
/ Centromere Protein A - ultrastructure
/ Centromeres
/ Chromatin
/ Chromosomal Proteins, Non-Histone - metabolism
/ Cryoelectron Microscopy
/ Deoxyribonucleic acid
/ DNA
/ DNA - chemistry
/ DNA - metabolism
/ DNA, Satellite - chemistry
/ DNA, Satellite - genetics
/ DNA, Satellite - metabolism
/ Gyres
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Kinetochores
/ Kinetochores - chemistry
/ Kinetochores - metabolism
/ Kinetochores - ultrastructure
/ Models, Molecular
/ Modules
/ multidisciplinary
/ Nucleosomes
/ Nucleosomes - chemistry
/ Nucleosomes - metabolism
/ Nucleosomes - ultrastructure
/ Nucleotide sequence
/ Satellite DNA
/ Science
/ Science (multidisciplinary)
/ Sequences
2026
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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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 82/80
/ 82/83
/ Arrays
/ Centromere Protein A - chemistry
/ Centromere Protein A - genetics
/ Centromere Protein A - metabolism
/ Centromere Protein A - ultrastructure
/ Chromosomal Proteins, Non-Histone - metabolism
/ DNA
/ Gyres
/ Histones
/ Humanities and Social Sciences
/ Humans
/ Kinetochores - ultrastructure
/ Modules
/ Nucleosomes - ultrastructure
/ Science
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