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Structure paper

タイトル	Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome.
ジャーナル・号・ページ	Nature, Vol. 574, Issue 7777, Page 278-282, Year 2019
掲載日	2019年10月2日
著者	Kaige Yan / Jing Yang / Ziguo Zhang / Stephen H McLaughlin / Leifu Chang / Domenico Fasci / Ann E Ehrenhofer-Murray / Albert J R Heck / David Barford /
PubMed 要旨	In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized ...In eukaryotes, accurate chromosome segregation in mitosis and meiosis maintains genome stability and prevents aneuploidy. Kinetochores are large protein complexes that, by assembling onto specialized Cenp-A nucleosomes, function to connect centromeric chromatin to microtubules of the mitotic spindle. Whereas the centromeres of vertebrate chromosomes comprise millions of DNA base pairs and attach to multiple microtubules, the simple point centromeres of budding yeast are connected to individual microtubules. All 16 budding yeast chromosomes assemble complete kinetochores using a single Cenp-A nucleosome (Cenp-A), each of which is perfectly centred on its cognate centromere. The inner and outer kinetochore modules are responsible for interacting with centromeric chromatin and microtubules, respectively. Here we describe the cryo-electron microscopy structure of the Saccharomyces cerevisiae inner kinetochore module, the constitutive centromere associated network (CCAN) complex, assembled onto a Cenp-A nucleosome (CCAN-Cenp-A). The structure explains the interdependency of the constituent subcomplexes of CCAN and shows how the Y-shaped opening of CCAN accommodates Cenp-A to enable specific CCAN subunits to contact the nucleosomal DNA and histone subunits. Interactions with the unwrapped DNA duplex at the two termini of Cenp-A are mediated predominantly by a DNA-binding groove in the Cenp-L-Cenp-N subcomplex. Disruption of these interactions impairs assembly of CCAN onto Cenp-A. Our data indicate a mechanism of Cenp-A nucleosome recognition by CCAN and how CCAN acts as a platform for assembly of the outer kinetochore to link centromeres to the mitotic spindle for chromosome segregation.
リンク	Nature / PubMed:31578520 / PubMed Central
手法	EM (単粒子)
解像度	3.45 - 4.15 Å
構造データ	4579 6qld EMDB-4579, PDB-6qld: Structure of inner kinetochore CCAN-Cenp-A complex 手法: EM (単粒子) / 解像度: 4.15 Å 4580 6qle EMDB-4580, PDB-6qle: Structure of inner kinetochore CCAN complex 手法: EM (単粒子) / 解像度: 3.55 Å 4581 6qlf EMDB-4581, PDB-6qlf: Structure of inner kinetochore CCAN complex with mask1 手法: EM (単粒子) / 解像度: 3.45 Å EMDB-4971: Structure of inner kinetochore CCAN complex 手法: EM (単粒子) / 解像度: 3.8 Å
由来	Saccharomyces cerevisiae (strain ATCC 204508 / S288c) cerevisiae (パン酵母) escherichia coli (大腸菌) saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母) saccharomyces cerevisiae (パン酵母)
キーワード	DNA BINDING PROTEIN (DNA結合タンパク質) / inner kinetochore / DNA (デオキシリボ核酸) / nucleosome (ヌクレオソーム) / CCAN / complex