Poly(ADP-ribose) mediates TRPS1 phase transition

TRPS1 has been identified as a participant in DNA repair and its assembly/disassembly is regulated by PARylation. However, the molecular principles and the physicochemical forces driving dynamic assembly/disassembly of TRPS1 in DNA damage repair (DDR) are remained enigmatic. In this study, we found that PARylation controls TRPS1 assembly/disassembly via forming Poly(ADP-ribose) (PAR) to bind TRPS1 to promote its phase separation. TRPS1 CTD together with its GATA domain is the molecular determinant region, and its NTD is the inhibitory region for TRPS1 phase separation. Our findings reveal PAR-mediated protein phase separation as organizing principle for sub-nucleus compartmentalization in DDR via linking protein phase transition to PARylation, DDRP spatiotemporal assembly/disassembly.