Mechanistic insight into anaphase bridge signaling to the abscission checkpoint.

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

SUBMITTER: Singh MI 

PROVIDER: S-EPMC12217976 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature