Defining a core configuration for human centromeres during mitosis

Ayantika Sen Gupta, Chris Seidel, Dai Tsuchiya, Sean McKinney, Zulin Yu, Sarah E. Smith, Jay R. Unruh and Jennifer L. Gerton ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42980-2

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