Condensin and topoisomerases cooperate to relieve topological stress at stalled replication forks

Abstract

Abstract Resolving complex topological structures at replication forks is essential for faithful DNA replication, yet the underlying mechanisms remain poorly understood. Evidence from diverse eukaryotes suggests that condensin – best known for driving chromosome condensation in mitosis – may also operate during S phase to alleviate torsional stress in cooperation with topoisomerases. Here, we show in budding yeast and human cells that condensin binds stressed replication forks, where it cooperates with topoisomerases I and II to promote nascent DNA resection and restart replication. Our data indicate that condensin acts together with topoisomerase I at reversed forks to convert positive supercoils into topological DNA structures that are relaxed by topoisomerase II, enabling fork restart. These findings reveal an evolutionarily conserved role for condensin in resolving topological constraints at arrested forks, reminiscent of its function in chromosome segregation, and suggest that this activity helps prevent the formation of toxic chromosome structures during fork arrest and reversal.