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

Natalie Laspata, Parminder Kaur, Sofiane Yacine Mersaoui, Daniela Muoio, Zhiyan Silvia Liu, Maxwell Henry Bannister, Hai Dang Nguyen, Caroline Curry, John M. Pascal, Guy G. Poirier, Hong Wang, Jean Yves Masson, Elise Fouquerel

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2215-2237
Number of pages23
JournalNucleic acids research
Volume51
Issue number5
DOIs
StatePublished - Mar 21 2023

Bibliographical note

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

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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