Opening of cohesin’s SMC ring is essential for timely DNA replication and DNA loop formation

Abstract

The ring-shaped cohesin complex topologically binds to DNA to establish sister chromatid cohesion. This topological binding creates a structural obstacle to genome-wide chromosomal events, such as replication. Here, we examine how conformational changes in cohesin circumvent being an obstacle in human cells. We show that ATP hydrolysis-driven head disengagement, leading to the structural maintenance of chromosome (SMC) ring opening, is essential for the progression of DNA replication. Closure of the SMC ring stalls replication in a checkpoint-independent manner. The SMC ring opening also facilitates sister chromatid resolution and chromosome segregation in mitosis. Single-molecule analyses reveal that forced closure of the SMC ring suppresses the translocation of cohesin on DNA as well as the formation of stable DNA loops. Our results suggest that the ATP hydrolysis-driven SMC ring opening makes topologically bound cohesin dynamic on DNA to achieve replication-dependent cohesion in the S phase and to resolve cohesion in mitosis. Thus, the SMC ring opening could be a fundamental mechanism to modulate both cohesion and higher-order genome structure.