Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules.
Kinetochores couple chromosomes to the mitotic spindle to segregate the genome during cell division. An error correction mechanism drives the turnover of kinetochore-microtubule attachments until biorientation is achieved. The structural basis for how kinetochore-mediated chromosome segregation is accomplished and regulated remains an outstanding question. In this work, we describe the ... cryo-electron microscopy structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. Complex assembly occurs through multiple interfaces, and a staple within Dam1 aids ring assembly. Perturbation of key interfaces suppresses yeast viability. Force-rupture assays indicated that this is a consequence of impaired kinetochore-microtubule attachment. The presence of error correction phosphorylation sites at Ndc80-Dam1 ring complex interfaces and the Dam1 staple explains how kinetochore-microtubule attachments are destabilized and reset.
Mesh Terms:
Cell Cycle Proteins, Chromosome Segregation, Cryoelectron Microscopy, Kinetochores, Microtubule-Associated Proteins, Microtubules, Protein Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Cell Cycle Proteins, Chromosome Segregation, Cryoelectron Microscopy, Kinetochores, Microtubule-Associated Proteins, Microtubules, Protein Conformation, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Science
Date: Dec. 08, 2023
PubMed ID: 38060647
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