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 genetic depletion causes an accumulation of unresolved R-loops which promotes genomic instability. Our study reveals that PARP1 is a novel sensor for R-loops and highlights that PARP1 is a suppressor of R-loop-associated genomic instability.
Laspata, Natalie; Kaur, Parminder; Mersaoui, Sofiane Yacine; Muoio, Daniela; Liu, Zhiyan Silvia; Bannister, Maxwell Henry; Nguyen, Hai Dang; Curry, Caroline; Pascal, John M.; Poirier, Guy G.; Wang, Hong; Masson, Jean-Yves; and Fouquerel, Elise, "PARP1 Associates With R-Loops to Promote Their Resolution and Genome Stability" (2023). Student Papers, Posters & Projects. Paper 100.
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