Formation of a dynamic kinetochore- microtubule interface through assembly of the Dam1 ring complex

Mol Cell. 2005 Jan 21;17(2):277-90. doi: 10.1016/j.molcel.2004.12.019.

Abstract

How kinetochore proteins form a dynamic interface with microtubules is largely unknown. In budding yeast, the 10-protein Dam1 complex is an Aurora kinase target that plays essential roles maintaining the integrity of the mitotic spindle and regulating interactions with the kinetochore. Here, we investigated the biochemical properties of purified Dam1 complex. The complex oligomerized into rings around microtubules. Ring formation was facilitated by microtubules but could occur in their absence. Mutant alleles led to partially assembled complexes or reduced microtubule binding. The interaction between rings and microtubules is mediated by the C termini of both Dam1 and alphabeta-tubulin. Ring formation promotes microtubule assembly, stabilizes against disassembly, and promotes bundling. A GTP-tubulin lattice is the preferred binding partner for the complex, and Dam1 rings can exhibit lateral mobility on microtubules. These observations suggest a mechanism by which the kinetochore can recognize and stay attached to the plus ends of microtubules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cattle
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / isolation & purification
  • Cell Cycle Proteins / metabolism*
  • Cytoskeletal Proteins
  • Guanosine Triphosphate / analogs & derivatives
  • Guanosine Triphosphate / metabolism
  • Hydrazines / metabolism
  • Kinetochores / metabolism*
  • Macromolecular Substances
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / isolation & purification
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Microtubules / ultrastructure
  • Models, Molecular
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Tubulin / genetics
  • Tubulin / metabolism

Substances

  • Alexa 488 hydrazide
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DAM1 protein, S cerevisiae
  • DUO1 protein, S cerevisiae
  • Hydrazines
  • Macromolecular Substances
  • Microtubule-Associated Proteins
  • Protein Subunits
  • Saccharomyces cerevisiae Proteins
  • Tubulin
  • Guanosine Triphosphate