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

Da Mota, M.; Delamarre, A.; Barthe, A.; Jackson, J.; Toran-Vilarrubias, A.; Ribeyre, C.; Vindigni, A.; Lin, Y.-L.; Pasero, P.; Lengronne, A.

doi:10.1101/2025.08.06.668895

bioRxiv · 10.1101/2025.08.06.668895

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

Da Mota, M.·Delamarre, A.·Barthe, A.·Jackson, J.·Toran-Vilarrubias, A.·Ribeyre, C.·Vindigni, A.·Lin, Y.-L.·Pasero, P.·Lengronne, A.

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Abstract

Resolving complex topological structures at replication forks is vital for successful DNA replication, but the mechanisms are little understood. Evidence from diverse eukaryotes suggests that condensin - which promotes chromosome condensation in M phase - might also act during S phase to facilitate relaxation of torsional stress by topoisomerases. Here, we show in yeast and human cells that condensin binds stressed replication forks, where it cooperates with topoisomerases I and II to promote resection of the nascent DNA and restart replication. Our findings suggest that condensin acts with topoisomerase I at reversed forks to convert positively supercoiled DNA into structures that are subsequently relaxed by topoisomerase 2, allowing the fork to resume replication. These findings uncover an important, evolutionarily conserved role for condensin in handling topological constraints at arrested forks that is reminiscent of its function in chromosome segregation and might prevent formation of toxic chromosome structures during fork arrest and reversal.

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Da Mota, M., Delamarre, A., Barthe, A., Jackson, J., Toran-Vilarrubias, A., Ribeyre, C., Vindigni, A., Lin, Y.-L., Pasero, P., Lengronne, A.. 2025-08-09. Condensin and topoisomerases cooperate to relieve topological stress at stalled replication forks. https://doi.org/10.1101/2025.08.06.668895

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