Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences
Previously, we reconstituted a minimal functional kinetochore from recombinant Saccharomyces cerevisiae 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 pat...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-05-01
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| Online Access: | https://elifesciences.org/articles/105150 |
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| author | Elise Miedlar Grace E Hamilton Samuel R Witus Sara J Gonske Michael Riffle Alex Zelter Rachel E Klevit Charles L Asbury Yoana N Dimitrova Trisha N Davis |
| author_facet | Elise Miedlar Grace E Hamilton Samuel R Witus Sara J Gonske Michael Riffle Alex Zelter Rachel E Klevit Charles L Asbury Yoana N Dimitrova Trisha N Davis |
| author_sort | Elise Miedlar |
| collection | DOAJ |
| description | Previously, we reconstituted a minimal functional kinetochore from recombinant Saccharomyces cerevisiae 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. |
| format | Article |
| id | doaj-art-7ed477a8eebd48dca281955dbe5dfc73 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-7ed477a8eebd48dca281955dbe5dfc732025-08-20T03:22:19ZengeLife Sciences Publications LtdeLife2050-084X2025-05-011410.7554/eLife.105150Force transmission through the inner kinetochore is enhanced by centromeric DNA sequencesElise Miedlar0https://orcid.org/0009-0009-8209-5210Grace E Hamilton1https://orcid.org/0000-0002-0522-0702Samuel R Witus2https://orcid.org/0000-0003-1907-8484Sara J Gonske3https://orcid.org/0009-0003-5491-9469Michael Riffle4https://orcid.org/0000-0003-1633-8607Alex Zelter5https://orcid.org/0000-0002-5331-0577Rachel E Klevit6https://orcid.org/0000-0002-3476-969XCharles L Asbury7https://orcid.org/0000-0002-0143-5394Yoana N Dimitrova8Trisha N Davis9https://orcid.org/0000-0003-4797-3152Department of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesDepartment of Neurobiology and Biophysics, University of Washington, Seattle, United StatesDepartment of Structural Biology, Genentech, Inc, South San Francisco, United StatesDepartment of Biochemistry, University of Washington, Seattle, United StatesPreviously, we reconstituted a minimal functional kinetochore from recombinant Saccharomyces cerevisiae 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.https://elifesciences.org/articles/105150mitosiscentromerekinetochoremicrotubuletensionnucleosome |
| spellingShingle | Elise Miedlar Grace E Hamilton Samuel R Witus Sara J Gonske Michael Riffle Alex Zelter Rachel E Klevit Charles L Asbury Yoana N Dimitrova Trisha N Davis Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences eLife mitosis centromere kinetochore microtubule tension nucleosome |
| title | Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences |
| title_full | Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences |
| title_fullStr | Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences |
| title_full_unstemmed | Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences |
| title_short | Force transmission through the inner kinetochore is enhanced by centromeric DNA sequences |
| title_sort | force transmission through the inner kinetochore is enhanced by centromeric dna sequences |
| topic | mitosis centromere kinetochore microtubule tension nucleosome |
| url | https://elifesciences.org/articles/105150 |
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