Bridging-induced phase separation induced by cohesin SMC protein complexes

Area of Science:

• Molecular Biology
• Genetics
• Biophysics

Background:

• Structural maintenance of chromosome (SMC) protein complexes, like cohesin, are known to extrude DNA loops.
• While loop extrusion is crucial for chromosome structure, other mechanisms may also contribute to genome organization.

Purpose of the Study:

• To investigate the behavior of yeast cohesin on DNA beyond loop extrusion.
• To explore the potential role of biomolecular condensation in cohesin-DNA interactions and genome organization.

Main Methods:

• In vitro experiments to observe DNA-cohesin clustering and liquid-like properties (fusion, FRAP, exchange).
• DNA length-dependent assays to determine clustering thresholds.
• In vivo studies in yeast cells to correlate findings with chromatin association.

Main Results:

• Yeast cohesin exhibits pronounced clustering on DNA, displaying characteristics of biomolecular condensation.
• These DNA-cohesin clusters show liquid-like behavior, including fusion and exchange with the environment.
• Clustering is dependent on DNA length, occurring only on DNA exceeding 3 kilobase pairs.
• Bridging-induced phase separation is proposed as the mechanism, involving DNA-cohesin-DNA bridges.

Conclusions:

• Biomolecular condensation, specifically bridging-induced phase separation, is a novel mechanism for cohesin-DNA interaction.
• This condensation process influences genome organization by SMC proteins.
• A fraction of cohesin in yeast cells associates with chromatin consistent with this phase separation model.