ArticleNucleic acids research2014
Processing of double-R-loops in (CAG)·(CTG) and C9orf72 (GGGGCC)·(GGCCCC) repeats causes instability.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 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
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
72 citing papers in PubMed, 118 citations in OpenAlex.
- Multi-hit genetic lesions and a stress-imprinted immune transcriptome define the inflammatory pathology in ALS patients.Research square · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Article
- Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.Nature reviews. Neurology · 2025Review
- RNA/DNA-binding protein TDP43 regulates DNA mismatch repair genes with implications for genome stability.Nucleic acids research · 2025Article
- RNA/DNA Binding Protein TDP43 Regulates DNA Mismatch Repair Genes with Implications for Genome Stability.bioRxiv : the preprint server for biology · 2025Article
- Base editing of trinucleotide repeats that cause Huntington's disease and Friedreich's ataxia reduces somatic repeat expansions in patient cells and in mice.Nature genetics · 2025Article
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- Beyond the Synapse:International journal of molecular sciences · 2024Review
- The hidden architects of the genome: a comprehensive review of R-loops.Molecular biology reports · 2024Review
- Chromosomal R-loops: who R they?Biologia futura · 2024Review
- R-LOOPs on Short Tandem Repeat Expansion Disorders in Neurodegenerative Diseases.Molecular neurobiology · 2023Review
- Structure and Dynamics of DNA and RNA Double Helices Formed by d(CTG), d(GTC), r(CUG), and r(GUC) Trinucleotide Repeats and Associated DNA-RNA Hybrids.The journal of physical chemistry. B · 2023Article
- A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1Cell & bioscience · 2023Article
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- 5hmC modification regulates R-loop accumulation in response to stress.Frontiers in psychiatry · 2023Article
- The RNA export and RNA decay complexes THO and TRAMP prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions.PLoS biology · 2022Article
- Review
- Walking a tightrope: The complex balancing act of R-loops in genome stability.Molecular cell · 2022Review
- Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Many of these repeats are bidirectionally transcribed, allowing for single- and double-R-loop configurations, where either or both DNA strands may be RNA-bound. R-loops can trigger repeat instability at (CTG)·(CAG) repeats, but the mechanism of this is unclear. We demonstrate R-loop-mediated instability through processing of R-loops by HeLa and human neuron-like cell extracts. Double-R-loops induced greater instability than single-R-loops. Pre-treatment with RNase H only partially suppressed instability, supporting a model in which R-loops directly generate instability by aberrant processing, or via slipped-DNA formation upon RNA removal and its subsequent aberrant processing. Slipped-DNAs were observed to form following removal of the RNA from R-loops. Since transcriptionally-induced R-loops can occur in the absence of DNA replication, R-loop processing may be a source of repeat instability in the brain. Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)·(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. These findings provide a mechanistic basis for R-loop-mediated instability at disease-associated repeats.
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What OpenQuestion holds
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.