Transient Poly(ADP-Ribose) Triggers FUS Condensation Hysteresis via a Prion-Like Mechanism.

ABSTRACT: Hysteresis-where a system retains memory of a transient stimulus-is common in signaling but can also arise in intracellular organization. DNA repair foci, a type of biomolecular condensate, are initiated by the short-lived noncanonical nucleic acid poly(ADP-ribose) (PAR). PAR recruits proteins with prion-like domains (PrLDs), such as Fused in Sarcoma (FUS), and initiates their condensation, which persists even after PAR degradation. How FUS transitions from PAR-dependent to PAR-independent condensation remains unclear. Here, we show that PAR binding triggers a conformational switch in FUS, enabling sustained condensation. PAR binds to the C-terminal arginine-rich region of FUS, displacing intramolecular contacts, and exposing the N-terminal PrLD. This conformational opening allows PrLD int

SUBMITTER: Liu H 

PROVIDER: S-EPMC12236490 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature