Fig. 2

Cohesin activity during interphase. a Schematic of cohesin loop extrusion (LE) cycle (i–vii), Wapl-dependent termination of LE (viii–xii), and Wapl-dependent cohesin unloading (xiii–xv). Note that Scc2-catalyzed LE does not involve topological entrapment. One possible variant of cohesin structural rearrangements accompanying the LE cycle is depicted. This specific scenario involves (as was largely proposed by other authors [37, 42, 43]) cycles of cohesin bending–unbending at elbow regions of SMC coiled-coils coupled with cycles of ATP binding-hydrolysis and SMC head engagement–disengagement. During the LE cycle, the cohesin molecule constantly maintains DNA binding through one DNA-binding surface (stable anchor) while translocating along DNA with the other two DNA-interacting domains (dynamic anchor). Here, we propose that the stable DNA-binding surface is represented by Scc3, whereas DNA is transiently captured by either SMC heads and Scc2 in “gripping state” or hinge domains. LE can be terminated by Pds5–Wapl-catalyzed DNA passage through the Smc3–kleisin gate (xii), which leads to topological DNA entrapment. Note that CTCF blocks Pds5-dependent Wapl recruitment. Additional round of the gate opening (in essence a reverse reaction, catalyzed by the same protein complex) unloads cohesin from DNA and destroys the chromatin loop (xiv). The latter is inhibited in the G2 phase by Smc3 K112/113 acetylation and Sororin. b Hypothetical structure of CTCF-defined chromatin loop. CTCF stabilizes cohesin in the depicted conformation by promoting Pds5 binding to the complex while blocking Scc2 and Wapl recruitment. Potential propensity of asymmetrically extruding SMC complexes to form closely spaced dimmers [44] can explain formation of loops with CTCF bound to both external anchors