2023 article

PARP1 associates with R-loops to promote their resolution and genome stability

Laspata, N., Kaur, P., Mersaoui, S. Y., Muoio, D., Liu, Z. S., Bannister, M. H., … Fouquerel, E. (2023, February 16). NUCLEIC ACIDS RESEARCH.

By: N. Laspata*, P. Kaur*, S. Mersaoui*, D. Muoio*, Z. Liu*, M. Bannister*, H. Nguyen*, C. Curry* ...

MeSH headings : Humans; DNA / chemistry; DNA Repair; Genomic Instability; Poly (ADP-Ribose) Polymerase-1 / genetics; Poly (ADP-Ribose) Polymerase-1 / metabolism; R-Loop Structures; RNA / chemistry
Source: Web Of Science
Added: March 20, 2023

Abstract 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.