A Structure-Based Mechanism for DNA Entry into the Cohesin Ring.

Area of Science:

• Molecular Biology
• Structural Biology
• Genetics

Background:

• Cohesin complexes are crucial for sister chromatid cohesion and chromosome organization.
• The precise mechanism of cohesin ring loading onto DNA remains largely unknown.

Purpose of the Study:

• To elucidate the molecular mechanism of cohesin loading onto DNA.
• To visualize the intermediate structures involved in the cohesin-DNA interaction.

Main Methods:

• Biochemical approaches
• Cryo-electron microscopy (cryo-EM) to visualize structural intermediates.

Main Results:

• A cohesin loading intermediate was visualized with DNA trapped between two gates.
• The kleisin gate opens upon ATP binding, and the ATPase gate opens upon ATP hydrolysis.
• A conserved kleisin N-terminal tail may dictate loading success or loop extrusion.

Conclusions:

• The study establishes the molecular basis for cohesin loading onto DNA.
• The findings provide a structural framework for understanding cohesin's role in genome stability.