Nonlinear mechanics of human mitotic chromosomes

Anna E. C. Meijering, Kata Sarlós, Christian F. Nielsen, Hannes Witt, Janni Harju, Emma Kerklingh, Guus H. Haasnoot, Anna H. Bizard, Iddo Heller, Chase P. Broedersz (), Ying Liu, Erwin J. G. Peterman, Ian D. Hickson () and Gijs J. L. Wuite ()
Additional contact information
Anna E. C. Meijering: Vrije Universiteit Amsterdam
Kata Sarlós: University of Copenhagen
Christian F. Nielsen: University of Copenhagen
Hannes Witt: Vrije Universiteit Amsterdam
Janni Harju: Vrije Universiteit Amsterdam
Emma Kerklingh: Vrije Universiteit Amsterdam
Guus H. Haasnoot: Vrije Universiteit Amsterdam
Anna H. Bizard: University of Copenhagen
Iddo Heller: Vrije Universiteit Amsterdam
Chase P. Broedersz: Vrije Universiteit Amsterdam
Ying Liu: University of Copenhagen
Erwin J. G. Peterman: Vrije Universiteit Amsterdam
Ian D. Hickson: University of Copenhagen
Gijs J. L. Wuite: Vrije Universiteit Amsterdam

Nature, 2022, vol. 605, issue 7910, 545-550

Abstract: Abstract In preparation for mitotic cell division, the nuclear DNA of human cells is compacted into individualized, X-shaped chromosomes1. This metamorphosis is driven mainly by the combined action of condensins and topoisomerase IIα (TOP2A)2,3, and has been observed using microscopy for over a century. Nevertheless, very little is known about the structural organization of a mitotic chromosome. Here we introduce a workflow to interrogate the organization of human chromosomes based on optical trapping and manipulation. This allows high-resolution force measurements and fluorescence visualization of native metaphase chromosomes to be conducted under tightly controlled experimental conditions. We have used this method to extensively characterize chromosome mechanics and structure. Notably, we find that under increasing mechanical load, chromosomes exhibit nonlinear stiffening behaviour, distinct from that predicted by classical polymer models4. To explain this anomalous stiffening, we introduce a hierarchical worm-like chain model that describes the chromosome as a heterogeneous assembly of nonlinear worm-like chains. Moreover, through inducible degradation of TOP2A5 specifically in mitosis, we provide evidence that TOP2A has a role in the preservation of chromosome compaction. The methods described here open the door to a wide array of investigations into the structure and dynamics of both normal and disease-associated chromosomes.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04666-5 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:605:y:2022:i:7910:d:10.1038_s41586-022-04666-5

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04666-5

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().