The Cohesin complex that holds sister chromatins together until anaphase is comprised of three core subunits: Smc1 and Smc3, two long-rod-shaped proteins with an ABC-like ATPase head (nucleotide-binding domain [NBD]) and a dimerization domain linked by a 50 nm long intramolecular antiparallel coiled-coil, and Scc1, an α-kleisin subunit interconnecting the NBD domains of Smc1 and Smc3. Cohesin's stable association with chromosomes is thought to involve entrapment of chromatin fibers by its tripartite Smc1-Smc3-Scc1 ring via a poorly understood mechanism dependent on a separate Scc2/4 loading complex. A key issue concerns where entrapment initially takes place: at sites where cohesin is found stably associated or at distinct "loading" sites from which it translocates.
We are grateful to Nasmyth lab members for useful discussions, R. Parton for help with microscopy, K. Nakagawa for ChIP-SEQ, B. Panaretou and K. Bloom for providing useful yeast strains and plasmids, and S. Gruber for critical reading of the manuscript. T.I. and Y.K. were supported by Grant-in-Aid for Young Scientists (A) from MEXT. K.S. was supported by a grant of the Cell Innovation Program and Grant-in-Aid for Scientific Research (S) from the MEXT, Japan. K.N. was supported by Cancer Research UK and the Wellcome Trust.