Abstract
SummaryKinetochores 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.
Highlights
The kinetochore is a multi-molecular machine that links centromeric nucleosomes to microtubules for chromosome segregation.[1]
Centromere, and Kinetochore Proteomes To reveal the changes in centromeric chromatin composition that underlie its specialized functions during meiosis, we analyzed the proteome of minichromosomes isolated from budding yeast cells at different cell-cycle stages
We immunoprecipitated LacI-FLAG bound to lacO arrays on a circular minichromosome carrying the budding yeast centromere 3 (CEN3) sequence (Figure 1A; CEN chromatin).[33]
Summary
The kinetochore is a multi-molecular machine that links centromeric nucleosomes to microtubules for chromosome segregation.[1] In budding yeast, sequence-specific binding of the Cbf[3] complex (Cbf3c) enables formation of a single Cse4CENP-A-containing nucleosome,[2] which directly contacts Mif2CENP-C and components of the inner kinetochore 13-subunit Ctf[19] complex (Ctf19c, known as CCAN in humans).[3–9]. Mif2CENP-C and Ctf19cCCAN form independent links to the 4-subunit Mtw[1] complex (Mtw1cMIS12c, known as MIND), forming the core of the kinetochore.[5,10–13]. The specialized cell division that generates gametes, kinetochores adopt additional roles. These include non-homologous centromere coupling, repression of meiotic recombination, and co-segregation of sister chromatids in meiosis I.24. These include non-homologous centromere coupling, repression of meiotic recombination, and co-segregation of sister chromatids in meiosis I.24 Uniquely during meiotic prophase, the outer kinetochore
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