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Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. | LitMetric

AI Article Synopsis

  • Accurate chromosome segregation in eukaryotes, particularly during mitosis and meiosis, is essential for maintaining genome stability and preventing conditions like aneuploidy.
  • Kinetochores, which are protein complexes that form on Cenp-A nucleosomes, connect centromeric DNA to microtubules, playing a crucial role in the movement of chromosomes.
  • This study presents the cryo-electron microscopy structure of the inner kinetochore module in budding yeast, detailing how the CCAN complex interacts with Cenp-A, revealing mechanisms for its assembly and linking to the mitotic spindle for effective chromosome segregation.

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859074PMC
http://dx.doi.org/10.1038/s41586-019-1609-1DOI Listing

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