PARP1-DNA co-condensation drives DNA repair site assembly to prevent disjunction of broken DNA ends

Research output: Contribution to journalResearch articleContributedpeer-review



DNA double-strand breaks (DSBs) are repaired at DSB sites. How DSB sites assemble and how broken DNA is prevented from separating is not understood. Here we uncover that the synapsis of broken DNA is mediated by the DSB sensor protein poly(ADP-ribose) (PAR) polymerase 1 (PARP1). Using bottom-up biochemistry, we reconstitute functional DSB sites and show that DSB sites form through co-condensation of PARP1 multimers with DNA. The co-condensates exert mechanical forces to keep DNA ends together and become enzymatically active for PAR synthesis. PARylation promotes release of PARP1 from DNA ends and the recruitment of effectors, such as Fused in Sarcoma, which stabilizes broken DNA ends against separation, revealing a finely orchestrated order of events that primes broken DNA for repair. We provide a comprehensive model for the hierarchical assembly of DSB condensates to explain DNA end synapsis and the recruitment of effector proteins for DNA damage repair.


Original languageEnglish
Pages (from-to)945-961.e18
Number of pages35
Volume187 (2024)
Issue number4
Early online date31 Jan 2024
Publication statusPublished - 15 Feb 2024

External IDs

unpaywall 10.1016/j.cell.2024.01.015
ORCID /0000-0003-4017-6505/work/153110458
Mendeley fe66f066-68d7-3172-a403-a6879b053505
Scopus 85185346177



  • DNA/metabolism, DNA Repair, Humans, Poly (ADP-Ribose) Polymerase-1/genetics, DNA Damage, DNA Breaks, Double-Stranded