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Defining a core configuration for human centromeres during mitosis

Author

Listed:
  • Ayantika Sen Gupta

    (Stowers Institute for Medical Research)

  • Chris Seidel

    (Stowers Institute for Medical Research)

  • Dai Tsuchiya

    (Stowers Institute for Medical Research)

  • Sean McKinney

    (Stowers Institute for Medical Research)

  • Zulin Yu

    (Stowers Institute for Medical Research)

  • Sarah E. Smith

    (Stowers Institute for Medical Research)

  • Jay R. Unruh

    (Stowers Institute for Medical Research)

  • Jennifer L. Gerton

    (Stowers Institute for Medical Research
    University of Kansas)

Abstract

The centromere components cohesin, CENP-A, and centromeric DNA are essential for biorientation of sister chromatids on the mitotic spindle and accurate sister chromatid segregation. Insight into the 3D organization of centromere components would help resolve how centromeres function on the mitotic spindle. We use ChIP-seq and super-resolution microscopy with single particle averaging to examine the geometry of essential centromeric components on human chromosomes. Both modalities suggest cohesin is enriched at pericentromeric DNA. CENP-A localizes to a subset of the α-satellite DNA, with clusters separated by ~562 nm and a perpendicular intervening ~190 nM wide axis of cohesin in metaphase chromosomes. Differently sized α-satellite arrays achieve a similar core structure. Here we present a working model for a common core configuration of essential centromeric components that includes CENP-A nucleosomes, α-satellite DNA and pericentromeric cohesion. This configuration helps reconcile how centromeres function and serves as a foundation to add components of the chromosome segregation machinery.

Suggested Citation

  • Ayantika Sen Gupta & Chris Seidel & Dai Tsuchiya & Sean McKinney & Zulin Yu & Sarah E. Smith & Jay R. Unruh & Jennifer L. Gerton, 2023. "Defining a core configuration for human centromeres during mitosis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42980-2
    DOI: 10.1038/s41467-023-42980-2
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    References listed on IDEAS

    as
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    2. Flora Paldi & Bonnie Alver & Daniel Robertson & Stephanie A. Schalbetter & Alastair Kerr & David A. Kelly & Jonathan Baxter & Matthew J. Neale & Adele L. Marston, 2020. "Convergent genes shape budding yeast pericentromeres," Nature, Nature, vol. 582(7810), pages 119-123, June.
    3. Kozo Tanaka & Naomi Mukae & Hilary Dewar & Mark van Breugel & Euan K. James & Alan R. Prescott & Claude Antony & Tomoyuki U. Tanaka, 2005. "Molecular mechanisms of kinetochore capture by spindle microtubules," Nature, Nature, vol. 434(7036), pages 987-994, April.
    4. Lauren A. Harasymiw & Damien Tank & Mark McClellan & Neha Panigrahy & Melissa K. Gardner, 2019. "Centromere mechanical maturation during mammalian cell mitosis," Nature Communications, Nature, vol. 10(1), pages 1-21, December.
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