Cryo-EM structure of the complete inner kinetochore of the budding yeast point centromere.
The point centromere of budding yeast specifies assembly of the large kinetochore complex to mediate chromatid segregation. Kinetochores comprise the centromere-associated inner kinetochore (CCAN) complex and the microtubule-binding outer kinetochore KNL1-MIS12-NDC80 (KMN) network. The budding yeast inner kinetochore also contains the DNA binding centromere-binding factor 1 (CBF1) and CBF3 complexes. ... We determined the cryo-electron microscopy structure of the yeast inner kinetochore assembled onto the centromere-specific centromere protein A nucleosomes (CENP-ANuc). This revealed a central CENP-ANuc with extensively unwrapped DNA ends. These free DNA duplexes bind two CCAN protomers, one of which entraps DNA topologically, positioned on the centromere DNA element I (CDEI) motif by CBF1. The two CCAN protomers are linked through CBF3 forming an arch-like configuration. With a structural mechanism for how CENP-ANuc can also be linked to KMN involving only CENP-QU, we present a model for inner kinetochore assembly onto a point centromere and how it organizes the outer kinetochore for chromosome attachment to the mitotic spindle.
Mesh Terms:
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Centromere, Centromere Protein A, Chromosomal Proteins, Non-Histone, Cryoelectron Microscopy, DNA, Kinetochores, Nuclear Proteins, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Saccharomycetales
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Centromere, Centromere Protein A, Chromosomal Proteins, Non-Histone, Cryoelectron Microscopy, DNA, Kinetochores, Nuclear Proteins, Protein Subunits, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Saccharomycetales
Sci Adv
Date: Jul. 28, 2023
PubMed ID: 37506202
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