ArticleProceedings of the National Academy of Sciences of the United States of America2010
R loops stimulate genetic instability of CTG.CAG repeats.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers.
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Who cites it
131 citing papers in PubMed, 193 citations in OpenAlex.
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.Nature reviews. Neurology · 2025Review
- 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
- Review
- Transcription-Coupled Repair and R-Loop Crosstalk in Genome Stability.International journal of molecular sciences · 2025Review
- R-loops as a trigger for intra- and extrachromosomal DNA amplification in cancer.Frontiers in cell and developmental biology · 2025Review
- Fitness landscapes of human microsatellites.PLoS genetics · 2024Article
- Pathological R-loops in bacteria from engineered expression of endogenous antisense RNAs whose synthesis is ordinarily terminated by Rho.Nucleic acids research · 2024Article
- Cas9 nickase-mediated contractions of CAG/CTG repeats are transcription-dependent and replication-independent.NAR molecular medicine · 2024Article
- Article
- Simultaneous Visualization of R-Loops/RNA:DNA Hybrids and Replication Forks in a DNA Combing Assay.Genes · 2024Article
- Role of senataxin in R-loop-mediated neurodegeneration.Brain communications · 2024Review
- Review
- R-LOOPs on Short Tandem Repeat Expansion Disorders in Neurodegenerative Diseases.Molecular neurobiology · 2023Review
- MicrosatNavigator: exploring nonrandom distribution and lineage-specificity of microsatellite repeat motifs on vertebrate sex chromosomes across 186 whole genomes.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023Article
- 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
- TUG1-mediated R-loop resolution at microsatellite loci as a prerequisite for cancer cell proliferation.Nature communications · 2023Article
- Article
- Mutation and selection processes regulating short tandem repeats give rise to genetic and phenotypic diversity across species.Journal of evolutionary biology · 2023Review
- The RNA export and RNA decay complexes THO and TRAMP prevent transcription-replication conflicts, DNA breaks, and CAG repeat contractions.PLoS biology · 2022Article
71 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Transcription stimulates the genetic instability of trinucleotide repeat sequences. However, the mechanisms leading to transcription-dependent repeat length variation are unclear. We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts. In vitro transcribed CG-rich repeating sequences, unlike AT-rich repeats and nonrepeating sequences, form stable, ribonuclease A-resistant structures. These RNA.DNA hybrids are eliminated by ribonuclease H treatment. Mutation in the rnhA1 gene that decreases the activity of ribonuclease HI stimulates the instability of CTG.CAG repeats in E. coli. Importantly, the effect of ribonuclease HI depletion on repeat instability requires active transcription. We also showed that transcription-dependent CTG.CAG repeat instability in human cells is stimulated by siRNA knockdown of RNase H1 and H2. In addition, we used bisulfite modification, which detects single-stranded DNA, to demonstrate that the nontemplate DNA strand at transcribed CTG.CAG repeats remains partially single-stranded in human genomic DNA, thus indicating that it is displaced by an RNA.DNA hybrid. These studies demonstrate that persistent hybrids between the nascent RNA transcript and the template DNA strand at CTG.CAG tracts promote instability of DNA trinucleotide repeats.
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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.