Srs2/PARI DNA helicase mediates abscission inhibition in response to chromatin bridges in yeast and human cells

The coordination of chromosome segregation with cytokinesis is crucial for maintaining genomic stability. Chromatin bridges, arising from DNA replication stress or catenated chromosomes, can interfere with this process, leading to genomic instability if not properly managed. Here, we uncover that the budding yeast DNA helicase Srs2 and its human homolog PARI delay the timing of abscission events in the presence of chromatin bridges. We demonstrate that Srs2 is essential for delaying abscission in yeast cells with chromatin bridges, and preventing their damage by cytokinesis. In human cells, PARI similarly plays a key role in delaying abscission events, such as midbody severing and actin patch disassembly during cytokinesis, in response to chromatin bridges caused by topoisomerase II inhibition. Our results also show that PARI functions within the Aurora B-mediated abscission checkpoint pathway. These findings reveal an evolutionarily conserved role of the Srs2/PARI DNA helicase in maintaining genomic integrity by modulating abscission timing in response to chromatin bridge formation.