The Francis Crick Institute
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Mechanical disengagement of the cohesin ring.

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Version 2 2024-01-25, 09:53
Version 1 2023-10-30, 10:36
journal contribution
posted on 2024-01-25, 09:53 authored by Martina Richeldi, Georgii Pobegalov, Torahiko L Higashi, Karolina Gmurczyk, Frank Uhlmann, Maxim I Molodtsov
Cohesin forms a proteinaceous ring that is thought to link sister chromatids by entrapping DNA and counteracting the forces generated by the mitotic spindle. Whether individual cohesins encircle both sister DNAs and how cohesin opposes spindle-generated forces remains unknown. Here we perform force measurements on individual yeast cohesin complexes either bound to DNA or holding together two DNAs. By covalently closing the hinge and Smc3Psm3-kleisin interfaces we find that the mechanical stability of the cohesin ring entrapping DNA is determined by the hinge domain. Forces of ~20 pN disengage cohesin at the hinge and release DNA, indicating that ~40 cohesin molecules are sufficient to counteract known spindle forces. Our findings provide a mechanical framework for understanding how cohesin interacts with sister chromatids and opposes the spindle-generated tension during mitosis, with implications for other force-generating chromosomal processes including transcription and DNA replication.


Crick (Grant ID: CC2137, Grant title: Uhlmann CC2137) Crick (Grant ID: CC2125, Grant title: Molodtsov CC2125) European Research Council (Grant ID: 670412 - ChromatidCohesion, Grant title: ERC 670412 - ChromatidCohesion)