biostudies-literatureLaspata NNational Center for Advancing Translational SciencesP. Edward Evans FoundationNCATS NIH HHSThomas Jefferson UniversityNIEHS NIH HHSNHLBI NIH HHSTier I Canada Research Chair in DNA repair and Cancer TherapeuticsNational Institutes of HealthMerckUPMC Hillman Cancer Center and the Sydney Kimmel Cancer center at Thomas Jefferson UniversityNHLBINational Institute of HealthNIGMS NIH HHSMasonic Cancer Center, University of Minnesota2215-2237https://www.ebi.ac.uk/biostudies/studies/S-EPMC10018367biostudies-literatureUnknown51(5)PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA-DNA hybrid and a displaced non-template DNA strand. R-loops are involved in crucial physiological processes but can also be a source of genome instability if persistently unresolved. In this study, we demonstrate that PARP1 binds R-loops in vitro and associates with R-loop formation sites in cells which activates its ADP-ribosylation activity. Conversely, PARP1 inhibition or genetNucleic acids researchPARP1 associates with R-loops to promote their resolution and genome stability.PMC10018367UL1 TR002494R01HL163011FDN-388879UL1TR002494R00 ES027028R01 HL163011KL2 TR002492R00ES027028CIHR PJT-173370R01 GM123246KL2TR00249222-20-68-NGUYCIHR MOP-418863Mersaoui SYPoirier GGMuoio DKaur PBannister MHWang HLiu ZSCurry CPascal JMLaspata NMasson JYFouquerel ENguyen HDfalsePARP1 associates with R-loops to promote their resolution and genome stability.PARP1 is a DNA-dependent ADP-Ribose transferase with ADP-ribosylation activity that is triggered by DNA breaks and non-B DNA structures to mediate their resolution. PARP1 was also recently identified as a component of the R-loop-associated protein-protein interaction network, suggesting a potential role for PARP1 in resolving this structure. R-loops are three-stranded nucleic acid structures that consist of a RNA-DNA hybrid and a displaced non-template DNA strand. R-loops are involved in crucial physiological processes but can also be a source of genome instability if persistently unresolved. In this study, we demonstrate that PARP1 binds R-loops in vitro and associates with R-loop formation sites in cells which activates its ADP-ribosylation activity. Conversely, PARP1 inhibition or genet2023-01-01T00:00:00Z2023 Mar2025-04-22T08:41:46.183Z2025-04-05T22:41:15.312ZS-EPMC100183673679485310.1093/nar/gkad066