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PreprintCC BY-NC-NDbioRxiv

Mechanical characterization of human centromeres

  1. 1vrije universiteit amsterdam

Abstract

Centromeres must withstand high pulling forces in metaphase, yet allow rapid and complete chromosome segregation in anaphase. Using optical tweezers measurements on isolated human metaphase chromosomes, we find that centromeres are stiffer at low forces and more frequently exhibit pronounced softening compared to whole chromosomes, while displaying a similar stiffening response at high forces. We capture these mechanical properties by establishing a softened hierarchical worm-like chain model. Cohesin cleavage alters the mechanical properties of centromeres but does not lead to chromosome segregation in vitro. Topoisomerase II is recruited to centromeric regions under significant tension, likely to resolve the persistent centromeric DNA entanglements that provide additional sister chromatid cohesion. These findings advance our understanding of the mechanical resilience and regulation of centromeres during mitosis.

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BibTeX
@misc{clement2026mechanical,
  title = {{Mechanical characterization of human centromeres}},
  author = {T. Clement and C. F. Nielsen and Z. Liu and B. Hoogland and R. Cui and C. C. Caldwell and C. Broedersz and I. Hickson and G. Wuite},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.14.759046},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.14.759046v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - Mechanical characterization of human centromeres
AU  - T. Clement
AU  - C. F. Nielsen
AU  - Z. Liu
AU  - B. Hoogland
AU  - R. Cui
AU  - C. C. Caldwell
AU  - C. Broedersz
AU  - I. Hickson
AU  - G. Wuite
PY  - 2026
DA  - 2026/10/14
PB  - bioRxiv
DO  - 10.64898/2026.10.14.759046
UR  - https://www.biorxiv.org/content/10.64898/2026.10.14.759046v1
AB  - Centromeres must withstand high pulling forces in metaphase, yet allow rapid and complete chromosome segregation in anaphase. Using optical tweezers measurements on isolated human metaphase chromosomes, we find that centromeres are stiffer at low forces and more frequently exhibit pronounced softening compared to whole chromosomes, while displaying a similar stiffening response at high forces. We capture these mechanical properties by establishing a softened hierarchical worm-like chain model. Cohesin cleavage alters the mechanical properties of centromeres but does not lead to chromosome segregation in vitro. Topoisomerase II is recruited to centromeric regions under significant tension, likely to resolve the persistent centromeric DNA entanglements that provide additional sister chromatid cohesion. These findings advance our understanding of the mechanical resilience and regulation of centromeres during mitosis.
ER  -