Work

Roles of Srs2/PARI-family DNA helicases in NoCut checkpoint signaling and abscission regulation

Year: 2025

Type: article

Abstract: 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 resolved. Here, we uncover that the budding yeast DNA helicase Srs2 is essential for delaying abscission in the presence of chromatin bridges, thereby preventing chromosome breakage during cytokinesis. We also find that its human paralog PARI delays abscission-associated events, including midbody severing and actin-patch disassembly, in human cells with chromatin bridges. Although PARI depletion does not lead to increased bridge breakage or binucleation, our data indicate that PARI has nonessential functions within the Aurora B-mediated abscission checkpoint pathway. These findings establish a key role of Srs2 in NoCut checkpoint signaling in yeast, and suggest a functionally related role of PARI in coordinating abscission timing with chromatin bridge resolution in human cells.

Source: The Journal of Cell Biology

DOI: 10.1083/jcb.202502014

Authors: Monica Dam, David F. Moreno, Nicola Brownlow, Audrey Furst, Coralie Spiegelhalter, Manuel Mendoza