PARP-1 Activation Directs FUS to DNA Damage Sites to Form PARG-Reversible Compartments Enriched in Damaged DNA
Résumé
PARP-1 synthesizes long poly(ADP-ribose) chains(PAR) at DNA damage sites to recruit DNA repair fac-tors. Among proteins relocated on damaged DNA,the RNA-binding protein FUS is one of the mostabundant, raising the issue about its involvement inDNA repair. Here, we reconstituted the PARP-1/PAR/DNA systemin vitroand analyzed at the sin-gle-molecule level the role of FUS. We demonstratesuccessively the dissociation of FUS from mRNA,its recruitment at DNA damage sites through its bind-ing to PAR, and the assembly of damaged DNA-richcompartments. PARG, an enzyme family that hydro-lyzes PAR, is sufficient to dissociate damaged DNA-rich compartmentsin vitroand initiates the nucleocy-toplasmic shuttling of FUS in cells. We anticipatethat, consistent with previous models, FUS facilitatesDNA repair through the transient compartmentaliza-tion of DNA damage sites. The nucleocytoplasmicshuttling of FUS after the PARG-mediated compart-ment dissociation may participate in the formationof cytoplasmic FUS aggregates.
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(2019) PARP-1 Activation Directs FUS to DNA Damage Sites.pdf (5.84 Mo)
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