ArticleNature chemical biology2026
The PARP1-EXD2 axis orchestrates R-loop resolution to safeguard genome stability.
Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
8 citing papers in PubMed.
- R-loops in colorectal cancer: mechanisms, mapping strategies, and therapeutic opportunities.Molecular biology reports · 2026Review
- Dual and opposing roles of the EXD2 exonuclease in the resolution of RNA-DNA hybrids.Nucleic acids research · 2026Article
- Development of Selective PARP1 Inhibitors for the Treatment of Cancer.ACS medicinal chemistry letters · 2026Article
- Multi-omics dissection of R-loop dynamics in tumorigenesis: From transcription-replication conflict to therapeutic targets.Molecular therapy. Oncology · 2026Review
- Polymerase face-off: emerging concepts in transcription-replication coordination.EMBO reports · 2026Review
- Epigenetic consequences of DNA damage.Molecular cell · 2026Review
- Article
- PARPs and PARP inhibitors: molecular mechanisms and clinical applications.Molecular biomedicine · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors.
Funding
Abstract
R-loops, comprising an RNA-DNA hybrid and a displaced single-stranded DNA, are dynamic three-stranded nucleic acid structures that, when dysregulated, can disrupt transcription and replication, undermining genome integrity and contributing to human pathologies. Here we identify exonuclease 3'-5' domain-containing 2 (EXD2) as a pivotal R-loop resolvase. We demonstrate that EXD2, through direct interaction with poly(ADP-ribose) (PAR) polymers synthesized by R-loop-bound and activated PAR polymerase 1 (PARP1), is recruited to R-loops, where it undergoes acetylation by the acetyltransferase CREB-binding protein at K416. This modification increases EXD2's binding affinity toward R-loop structures, allowing stable association with these structures despite the rapid turnover of PAR polymers. Once retained, EXD2 preferentially degrades RNA strands within R-loops to promote their resolution. Loss of EXD2 results in the intracellular accumulation of R-loops, exacerbating transcription-replication conflicts and ultimately leading to genomic instability. These findings support a model in which R-loop-triggered PARP1 activation orchestrates EXD2-mediated resolution of R-loops, thereby preserving genome stability.
Indexed as
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.