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

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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Publication Details

Journal
eLife
Published
2025-02-21
DOI
https://doi.org/10.7554/elife.105150
Primary Topic
Microtubule and mitosis dynamics
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Yoana N. Dimitrova, Samuel R Witus, Trisha N. Davis, Grace E Hamilton et al.
eLife
Microtubule and mitosis dynamics
article

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

Yoana N. Dimitrova, Samuel R Witus, Trisha N. Davis, Grace E Hamilton, Alex Zelter, Rachel E. Klevit, Michael Riffle, Charles L. Asbury, Sara Gonske, Elise Miedlar
article en

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.

eLifeVol. 14
University of Washington (US)
National Institutes of Health
Life in Land
Openalex Percentile: Top 96%
Microtubule and mitosis dynamics
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Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences — Yoana N. Dimitrova, Samuel R Witus, et al. · eLife (2025) | TGRS Research Map | TGRS