In through the out door: A loop-binding-first model for topological cohesin loading

Cohesin is a ring-shaped complex that is loaded on DNA in two different conformations. In one conformation, it forms loops to organize the interphase genome; in the other, it topologically encircles sibling chromosomes to facilitate homologous recombination and to establish the cohesion that is required for orderly segregation during mitosis. How, and even if, these two loading conformation are related is unclear. Here, I propose that loop binding is a required first step for topological binding. This loop-binding-first model integrates the known information about the two loading mechanisms, explains genetic requirements for the two and explains how topological loading evolved from loop binding.