Work

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

Year: 2023

Type: article

Abstract: Kinetochores couple chromosomes to the mitotic spindle and transduce the energy of microtubule depolymerization to segregate the genome during cell division. Kinetochore – microtubule attachments are often initially erroneous and subject to a mitotic error correction (EC) mechanism that drives their turnover until biorientation is achieved. How this is accomplished and regulated, and how kinetochore-mediated chromosome segregation occurs at a molecular level remain major outstanding questions. Here we describe the cryo-electron microscopy (cryo-EM) structure of the budding yeast outer kinetochore Ndc80 and Dam1 ring complexes assembled onto microtubules. We observe coordinated interactions of the outer kinetochore complexes through multiple interfaces, in addition to a short staple within the Dam1 subunit that facilitates Dam1c ring assembly. Perturbation of these interfaces results in loss of yeast viability. Force-rupture assays indicated this is a consequence of substantial reductions in kinetochore – microtubule binding strength. EC-mediated phosphorylation of Ndc80c-Dam1c interfaces would drive complex disassembly, whereas Dam1 staple phosphorylation would promote Dam1c ring disassembly, explaining how kinetochore – microtubule attachments are destabilized and reset by the EC mechanism. One-Sentence Summary Phosphorylation disrupts the outer kinetochore to regulate kinetochore-microtubule attachments in mitotic error correction.

Source: Science

DOI: 10.1126/science.adj8736