The SMC1-SMC3 cohesin heterodimer structures DNA through supercoiling-dependent loop formation

Area of Science:

• Molecular Biology
• Biophysics
• Genetics

Background:

• Cohesin is vital for sister chromatid cohesion, DNA repair, and gene regulation.
• The precise mechanism of cohesin's direct interaction with DNA is not fully understood.

Purpose of the Study:

• To investigate the direct interaction between the budding yeast cohesin SMC1-SMC3 heterodimer and DNA.
• To elucidate the biophysical mechanism of DNA compaction by cohesin.

Main Methods:

• Single-molecule experiments were conducted to analyze the interaction of the SMC1-SMC3 heterodimer with double-helix DNA.
• DNA compaction was measured under applied forces, and the influence of DNA supercoiling and protein mutations was assessed.

Main Results:

• The SMC1-SMC3 heterodimer compacted DNA molecules, forming loops through discrete extension steps (≈130 nm).
• This compaction process was ATP-independent but sensitive to DNA supercoiling, with positive torsional stress accelerating the reaction.
• The dimerization hinge region of the protein was identified as critical for the DNA folding reaction.

Conclusions:

• The SMC1-SMC3 heterodimer can restructure DNA into loops, demonstrating a direct DNA interaction mechanism.
• Cohesin's DNA compaction activity is modulated by DNA topology, favoring positive writhe.