ArticleProceedings of the National Academy of Sciences of the United States of America2016
Pathological ribonuclease H1 causes R-loop depletion and aberrant DNA segregation in mitochondria.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Regulation of transcription by R loop-nucleated transcription condensate assembly.Cell & bioscience · 2026Review
- Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities.Nucleic acids research · 2026Article
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- Approaches for Mapping and Analysis of R-loops.Current protocols · 2024Review
- Live-cell imaging unveils distinct R-loop populations with heterogeneous dynamics.Nucleic acids research · 2023Article
- Regulation of Heat Stress inInternational journal of molecular sciences · 2022Article
- Walking a tightrope: The complex balancing act of R-loops in genome stability.Molecular cell · 2022Review
- NR4A1 regulates expression of immediate early genes, suppressing replication stress in cancer.Molecular cell · 2021Article
- Controlling the topology of mammalian mitochondrial DNA.Open biology · 2021Review
- BRCA2 deficiency reveals that oxidative stress impairs RNaseH1 function to cripple mitochondrial DNA maintenance.Cell reports · 2021Article
- Mitochondrial RNase H1 activity regulates R-loop homeostasis to maintain genome integrity and enable early embryogenesis in Arabidopsis.PLoS biology · 2021Article
- RNA: a double-edged sword in genome maintenance.Nature reviews. Genetics · 2020Review
- A second hybrid-binding domain modulates the activity of Drosophila ribonuclease H1.Journal of biochemistry · 2020Article
- Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses.Nature communications · 2019Article
- Replication Stress at Telomeric and Mitochondrial DNA: Common Origins and Consequences on Ageing.International journal of molecular sciences · 2019Review
- Review
- The mitochondrial R-loop.Nucleic acids research · 2019Article
- RNase H1 promotes replication fork progression through oppositely transcribed regions ofThe Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The genetic information in mammalian mitochondrial DNA is densely packed; there are no introns and only one sizeable noncoding, or control, region containing key cis-elements for its replication and expression. Many molecules of mitochondrial DNA bear a third strand of DNA, known as "7S DNA," which forms a displacement (D-) loop in the control region. Here we show that many other molecules contain RNA as a third strand. The RNA of these R-loops maps to the control region of the mitochondrial DNA and is complementary to 7S DNA. Ribonuclease H1 is essential for mitochondrial DNA replication; it degrades RNA hybridized to DNA, so the R-loop is a potential substrate. In cells with a pathological variant of ribonuclease H1 associated with mitochondrial disease, R-loops are of low abundance, and there is mitochondrial DNA aggregation. These findings implicate ribonuclease H1 and RNA in the physical segregation of mitochondrial DNA, perturbation of which represents a previously unidentified disease mechanism.
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