Formation of the clamped state by Scc2 and DNA overcomes the constraints imposed by zipping-up of the SMC coiled coils on cohesin's ATPase

In addition to mediating sister chromatid cohesion, cohesin, by virtue of Loop Extrusion (LE), organises the spatial arrangement of interphase DNA. The latter activity relies on DNA and Scc2 dependent ATP hydrolysis by cohesin. How the impetus from the ATPase cycle translates into reeling of DNA loops into the SMC kleisin rings is still unclear. The SMC coiled coils show several striking structural features like folding and zipping-up, if and how these structural states affect cohesins activity is still unclear. We show here that cohesins loop extruding motor contains an internal constraint that regulates its ATPase activity, zipping-up of the coiled coils impedes ATP hydrolysis by cohesin. We show that integrity of a region where the coiled coils emerge for the SMC hinge domains, SMC wrist, is critical for the zipping up of the coiled coils and the resulting inhibition of cohesins ATPase. Clamping of DNA by Scc2 onto the engaged SMC heads in the presence of ATP leads to unzipping of the coiled coils and permits ATP hydrolysis. Strikingly, irreversible folding of the coiled coils at the elbow region does not lead to any measurable change to the ATPase activity suggesting that recurrent cycles of folding and unfolding of the coiled coils is not necessary for driving continuous ATP hydrolysis by cohesin.