The Proteomic Landscape of Centromeric Chromatin Reveals an Essential Role for the Ctf19CCAN Complex in Meiotic Kinetochore Assembly

Curr Biol. 2021 Jan 25;31(2):283-296.e7. doi: 10.1016/j.cub.2020.10.025. Epub 2020 Nov 5.

Abstract

Kinetochores direct chromosome segregation in mitosis and meiosis. Faithful gamete formation through meiosis requires that kinetochores take on new functions that impact homolog pairing, recombination, and the orientation of kinetochore attachment to microtubules in meiosis I. Using an unbiased proteomics pipeline, we determined the composition of centromeric chromatin and kinetochores at distinct cell-cycle stages, revealing extensive reorganization of kinetochores during meiosis. The data uncover a network of meiotic chromosome axis and recombination proteins that bind to centromeres in the absence of the microtubule-binding outer kinetochore sub-complexes during meiotic prophase. We show that the Ctf19cCCAN inner kinetochore complex is essential for kinetochore organization in meiosis. Our functional analyses identify a Ctf19cCCAN-dependent kinetochore assembly pathway that is dispensable for mitotic growth but becomes critical upon meiotic entry. Therefore, changes in kinetochore composition and a distinct assembly pathway specialize meiotic kinetochores for successful gametogenesis.

Keywords: CCAN; Ctf19; budding yeast; centromere; kinetochore; meiosis; metaphase I; prophase I; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Centromere / metabolism*
  • Chromatin / metabolism*
  • Chromosome Segregation
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / isolation & purification
  • Cytoskeletal Proteins / metabolism*
  • Kinetochores / metabolism*
  • Meiosis*
  • Mitosis
  • Proteomics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Saccharomyces cerevisiae
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / isolation & purification
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • CTF19 protein, S cerevisiae
  • Chromatin
  • Cytoskeletal Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins