Organization of replicated chromosomes by DNA loops and sister chromatid cohesion

Cohesin is a key regulator of three-dimensional genome organization, contributing to gene regulation, recombination, DNA repair and chromosome segregation. Like other members of the evolutionary conserved structural maintenance of chromosomes (SMC) protein-complex family, cohesin folds DNA through motor-driven loop extrusion. Cohesin has a unique, second activity of genome organization: it physically links sister chromatids together in replicated chromosomes, a process termed sister chromatid cohesion. Sister chromatid cohesion and loop extrusion are mediated by two distinct pools of cohesin, which share common core subunits, but associate with distinct regulatory subunits to interact with chromosomes in fundamentally different ways. In this Review, we discuss how sister chromatid cohesion is established and regulated, and how an interplay between cohesion and chromatin loops organizes replicated chromosomes. We also discuss how cohesion supports chromosome segregation in mitosis and meiosis, and how it contributes to DNA double-strand break repair and age-related oocyte aneuploidy. We outline recent technological advances that provide new opportunities to study cohesion and the conformation of replicated chromosomes, and we provide a perspective on how these tools might be applied to answer fundamental questions in cohesin biology.