ArticleNature communications2023
The RNA m5C modification in R-loops as an off switch of Alt-NHEJ.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
30 citing papers in PubMed, 32 citations in OpenAlex.
- Quantitative profiling of RNA modifications enriched in non-membrane-bound cellular structures using APEX-RNA-MS.Cell chemical biology · 2026Article
- R-Loop Modification and Quantification by Dot Blot.Bio-protocol · 2026Article
- TRDMT1 slows lung cancer growth by stabilizing TFRC mRNA and triggering ferroptosis cell death.The Journal of biological chemistry · 2026Article
- Suppression of transcription-replication conflicts by sequence-coordinated actions of TRDMT1 and MutLα.Nature communications · 2026Article
- R-loops and D-loops: a delicate balance in genomic stability and instability.Cell communication and signaling : CCS · 2026Review
- Dynamic tRNA modification landscapes reveal METTL1 in fibroblasts as a central regulator of aging.Science China. Life sciences · 2026Article
- cGAS restricts PARP1-mediated microhomology-mediated end joining by suppressing poly-ADP-ribosylation.Cell death and differentiation · 2026Article
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- CBX2 phase-separation contributes to homologous recombination repair and drug resistance in ovarian cancer.Cell death & disease · 2026Article
- p53 status determines the epigenetic response to demethylating agents azacitidine and decitabine.EMBO reports · 2026Article
- NSUNs-driven dysregulation: the next frontier in targeted cancer therapy?Cell death & disease · 2025Review
- The multiple layers of RNA response in double-strand break repair.Experimental & molecular medicine · 2025Review
- Evolutionary interplay between viruses and R-loops.FEBS letters · 2025Review
- RNA 5-Methylcytosine Modification in Myocardial Fibrosis.Reviews in cardiovascular medicine · 2025Review
- Epigenetic Mechanisms Governing Nrf2 Expression and Its Role in Ferroptosis.Biomedicines · 2025Review
- Update on R-loops in genomic integrity: Formation, functions, and implications for human diseases.Genes & diseases · 2025Review
- Transcriptional repression facilitates RNA:DNA hybrid accumulation at DNA double-strand breaks.Nature cell biology · 2025Article
- RNA sculpting by the primordial Helix-clasp-Helix-Strand-Loop (HcH-SL) motif enforces chemical recognition enabling diverse KH domain functions.The Journal of biological chemistry · 2025Review
- Poly-(ADP-ribose) serves as a scaffold for the methyltransferase METTL3/14 complex in the DNA damage response.Nucleic acids research · 2025Article
- Epitranscriptomic mechanisms and implications of RNA mTheranostics · 2025Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The roles of R-loops and RNA modifications in homologous recombination (HR) and other DNA double-stranded break (DSB) repair pathways remain poorly understood. Here, we find that DNA damage-induced RNA methyl-5-cytosine (m5C) modification in R-loops plays a crucial role to regulate PARP1-mediated poly ADP-ribosylation (PARylation) and the choice of DSB repair pathways at sites of R-loops. Through bisulfite sequencing, we discover that the methyltransferase TRDMT1 preferentially generates m5C after DNA damage in R-loops across the genome. In the absence of m5C, R-loops activate PARP1-mediated PARylation both in vitro and in cells. Concurrently, m5C promotes transcription-coupled HR (TC-HR) while suppressing PARP1-dependent alternative non-homologous end joining (Alt-NHEJ), favoring TC-HR over Alt-NHEJ in transcribed regions as the preferred repair pathway. Importantly, simultaneous disruption of both TC-HR and Alt-NHEJ with TRDMT1 and PARP or Polymerase θ inhibitors prevents alternative DSB repair and exhibits synergistic cytotoxic effects on cancer cells, suggesting an effective strategy to exploit genomic instability in cancer therapy.
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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.