Bridging-induced phase separation induced by cohesin SMC protein complexes
Je Kyung Ryu (Kavli institute of nanoscience Delft, TU Delft - BN/Cees Dekker Lab)
Céline Bouchoux (Francis Crick Institute)
Hon Wing Liu (Francis Crick Institute)
Eugene Kim (TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)
Masashi Minamino (Francis Crick Institute)
Ralph de Groot (Kavli institute of nanoscience Delft, Student TU Delft)
Allard J. Katan (TU Delft - QN/Afdelingsbureau, Kavli institute of nanoscience Delft)
Andrea Bonato (The University of Edinburgh)
Davide Marenduzzo (The University of Edinburgh)
Davide Michieletto (The University of Edinburgh)
Frank Uhlmann (Francis Crick Institute)
Cees Dekker (TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)
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Abstract
Structural maintenance of chromosome (SMC) protein complexes are able to extrude DNA loops. While loop extrusion constitutes a fundamental building block of chromosomes, other factors may be equally important. Here, we show that yeast cohesin exhibits pronounced clustering on DNA, with all the hallmarks of biomolecular condensation. DNA-cohesin clusters exhibit liquid-like behavior, showing fusion of clusters, rapid fluorescence recovery after photobleaching and exchange of cohesin with the environment. Strikingly, the in vitro clustering is DNA length dependent, as cohesin forms clusters only on DNA exceeding 3 kilo-base pairs. We discuss how bridging-induced phase separation, a previously unobserved type of biological condensation, can explain the DNA-cohesin clustering through DNA-cohesin-DNA bridges. We confirm that, in yeast cells in vivo, a fraction of cohesin associates with chromatin in a manner consistent with bridging-induced phase separation. Biomolecular condensation by SMC proteins constitutes a new basic principle by which SMC complexes direct genome organization.