Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences.

Miedlar, Elise; Hamilton, Grace E; Witus, Samuel R; Gonske, Sara J; Riffle, Michael; Zelter, Alex; Klevit, Rachel E; Asbury, Charles L et al. · Elife · 2025

basic_science · Level V

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Abstract

Previously, we reconstituted a minimal functional kinetochore from recombinant <i>Saccharomyces cerevisiae</i> proteins that was capable of transmitting force from dynamic microtubules to nucleosomes containing the centromere-specific histone variant Cse4 (Hamilton et al., 2020). This work revealed two paths of force transmission through the inner kinetochore: through Mif2 and through the Okp1/Ame1 complex (OA). Here, using a chimeric DNA sequence that contains crucial centromere-determining elements of the budding yeast point centromere, we demonstrate that the presence of centromeric DNA sequences in Cse4-containing nucleosomes significantly strengthens OA-mediated linkages. Our findings indicate that centromeric sequences are important for the transmission of microtubule-based forces to the chromosome.

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