Structural mechanism of outer kinetochore Dam1-Ndc80 complex assembly on microtubules

Science. 2023 Dec 8;382(6675):1184-1190. doi: 10.1126/science.adj8736. Epub 2023 Dec 7.

Abstract

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* / chemistry
  • Chromosome Segregation
  • Cryoelectron Microscopy
  • Kinetochores*
  • Microtubule-Associated Proteins* / chemistry
  • Microtubules* / chemistry
  • Protein Conformation
  • Saccharomyces cerevisiae Proteins* / chemistry
  • Saccharomyces cerevisiae* / ultrastructure

Substances

  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • Saccharomyces cerevisiae Proteins
  • DAM1 protein, S cerevisiae
  • NDC80 protein, S cerevisiae