| Summary: | <p>Cohesin is essential for the spatial organization of the genome through its ability to extrude loops on the DNA. Structural information indicates that the cohesin’s Smcs fold at the elbow, bringing the hinge domain close to the ATPase heads and also can dissociate from each other to adopt an unzipped coils conformation. In all proposed loop extrusion models, cohesin needs to undergo changes to its conformational state, with unzipping or unfolding of the complex being necessary for its ATP hydrolysis driven loop extrusion. In this work, I investigate the role of cohesin’s conformation in relation to its ATPase activity. Specifically I am looking at its the folding and the zipping up of the coiled coils. I examine the changes that occur in those conformational states during cohesin’s ATP hydrolysis cycle while also considering their regulatory role. My research shows that both unzipping and unfolding occur during the hydrolysis cycle, while only unzipping is necessary for ATP hydrolysis. I find that the zipped-up coils inhibition is lost in cohesin trimers with mutations at the hinge that do not fold. The unfolded cohesin trimers hydrolyse ATP more readily than WT, indicating that the folded state is required for the stability of the zipping up of the coils. My results lead me to the conclusion that cohesin’s rigid APO state inhibits ATP hydrolysis due to the zipped up coils that are stabilized by the folding at the elbow. ATP hydrolysis therefore, requires Scc2 and DNA to ensure the unzipping of the coils in the clamped state. </p>
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