Summary
A bioRxiv preprint reports that centromeres in isolated human metaphase chromosomes have a distinct force response, including softening at some force levels. The researchers also found that topoisomerase IIα is recruited to centromeric regions under significant tension.
A bioRxiv preprint reports that human centromeres respond to mechanical force differently from whole chromosomes. Using optical tweezers on isolated human metaphase chromosomes, the researchers found that centromeres were stiffer at low forces, more often showed pronounced softening, and had a similar stiffening response to whole chromosomes at high forces.
Centromeres are chromosome regions that help coordinate the attachment and separation of duplicated chromosomes during cell division. They must maintain sister chromatids together while they are pulled in opposite directions, then allow those chromatids to separate. The study examines how their mechanical properties may contribute to that balance.
A force response that changes with tension
The researchers used an optical-tweezer method, which applies and measures forces using focused laser light, to characterize isolated metaphase chromosomes. They report that centromeres were stiffer than whole chromosomes at low forces, but more frequently underwent pronounced softening. At higher forces, centromeres and whole chromosomes showed a similar stiffening response.
The team described these measurements with a softened hierarchical worm-like chain model, a polymer-physics framework adapted to capture the observed mechanical behaviour. The findings suggest that centromere mechanics are not simply a scaled version of the chromosome as a whole: the response varies as applied force changes.
Cohesin, DNA entanglement and chromosome separation
The researchers also cleaved cohesin, a protein complex that helps hold sister chromatids together. This altered centromere mechanical properties, but did not cause chromosome segregation in the in-vitro experiments. The result indicates that changing cohesin alone was not sufficient to separate the chromatids in this setup.
The study further reports that topoisomerase IIα was recruited to centromeric regions under significant tension. The authors suggest that the enzyme may help resolve persistent DNA entanglements, which can provide additional cohesion between sister chromatids. This proposed role connects the measured response to a possible way cells manage the tension that builds during chromosome separation.
These results come from a preprint and experiments on isolated metaphase chromosomes, rather than observations of chromosome segregation in intact cells. They offer a mechanical characterization of centromeres and a basis for studying how protein-mediated cohesion and DNA entanglement contribute to chromosome behaviour.