ArticlePLoS genetics2019
RNase H1 directs origin-specific initiation of DNA replication in human mitochondria.
Article in PLoS genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 74 citations in OpenAlex.
- Cryptic DNA sequences encode a temperature sensor to regulate mitochondrial suicide during neuronal differentiation.Cell communication and signaling : CCS · 2026Article
- Human mitochondrial helicase Twinkle has RNA binding, annealing, and strand-exchange activities.Nucleic acids research · 2026Article
- Loss of lactate dehydrogenase A disrupts R-loop homeostasis and induces DNA damage in breast cancer cells.Frontiers in genetics · 2026Article
- Emerging roles of RNA:DNA hybrid regulation by mammalian ribonuclease H2 in replication stress and cancer.Journal of cell science · 2025Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- ebv-sisRNA-3 contributes to the formation of G4-associated R-loop upstream of EBV lytic replication origin in latently infected cells.Cell & bioscience · 2025Article
- A DNP-Supported Solid-State NMR Approach to Study Nucleic Acids In Situ Reveals Berberine-Stabilized Hoogsteen Structures in Mitochondria.Angewandte Chemie (International ed. in English) · 2025Article
- Mitochondrial DNA copy number alterations: Key players in the complexity of glioblastoma (Review).Molecular medicine reports · 2025Review
- TEFM facilitates transition from RNA synthesis to DNA synthesis at H-strand replication origin of mtDNA.Communications biology · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- The hidden architects of the genome: a comprehensive review of R-loops.Molecular biology reports · 2024Review
- Identification of the central role of RNA polymerase mitochondrial for angiogenesis.Cell communication and signaling : CCS · 2024Article
- Mechanisms and pathologies of human mitochondrial DNA replication and deletion formation.The Biochemical journal · 2024Review
- Mechanisms and regulation of human mitochondrial transcription.Nature reviews. Molecular cell biology · 2024Review
- TATDN2 resolution of R-loops is required for survival of BRCA1-mutant cancer cells.Nucleic acids research · 2023Article
- Cellular Responses to Widespread DNA Replication Stress.International journal of molecular sciences · 2023Review
- Article
- Identification of the mitochondrial protein POLRMT as a potential therapeutic target of prostate cancer.Cell death & disease · 2023Article
- Ribonucleotide and R-Loop Damage in Plastid DNA and Mitochondrial DNA during Maize Development.Plants (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Human mitochondrial DNA (mtDNA) replication is first initiated at the origin of H-strand replication. The initiation depends on RNA primers generated by transcription from an upstream promoter (LSP). Here we reconstitute this process in vitro using purified transcription and replication factors. The majority of all transcription events from LSP are prematurely terminated after ~120 nucleotides, forming stable R-loops. These nascent R-loops cannot directly prime mtDNA synthesis, but must first be processed by RNase H1 to generate 3'-ends that can be used by DNA polymerase γ to initiate DNA synthesis. Our findings are consistent with recent studies of a knockout mouse model, which demonstrated that RNase H1 is required for R-loop processing and mtDNA maintenance in vivo. Both R-loop formation and DNA replication initiation are stimulated by the mitochondrial single-stranded DNA binding protein. In an RNase H1 deficient patient cell line, the precise initiation of mtDNA replication is lost and DNA synthesis is initiated from multiple sites throughout the mitochondrial control region. In combination with previously published in vivo data, the findings presented here suggest a model, in which R-loop processing by RNase H1 directs origin-specific initiation of DNA replication in human mitochondria.
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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.