Mechanistic insight into anaphase bridge signaling to the abscission checkpoint

• DOI: 10.1038/s44318-025-00453-w
• Publication Date: 2025-05-12T15:11:39Z
• Authors: Manika I Singh; Girish Rajendrapr...; Vasileios Katopodis; Rui Cui; Marin Barisic; Rahul Bhowmick; Ian D Hickson
• Keywords: Spindle checkpoint; Bloom syndrome; Abscission; Chromosome instability; CHEK1; Aurora B kinase

Abstract During cytokinesis in human cells, a failure to resolve persistent DNA bridges that span the cell-division plane maintains Aurora B-dependent abscission checkpoint an active state. However, molecular mechanism by which unresolved sister-chromatid bridging signals this is poorly defined. Here, we define essential role for Bloom’s syndrome helicase, BLM, signaling abscission-checkpoint machinery response replication stress through conversion of dsDNA into RPA-coated ssDNA. RPA then promotes ATR-CHK1 B, utilizing kinase cascade shared with S-phase checkpoint. BLM-deficient cells ultimately abandon stress, binucleation and hence aneuploidy. Considering aneuploidy hallmark cancer, propose BLM plausible reason cancer predisposition individuals. Consistent this, deficiency anchorage-independent growth non-cancer cells.