Document Type

Article

Publication Date

2-16-2023

Comments

This article is the author's final published version in Nucleic Acids Research, Volume 51, Issue 5, 21 March 2023, Pg. 2215 - 2237.

The published version is available at https://doi.org/10.1093/nar/gkad066.

Copyright © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research

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.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Language

English

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