ArticlePLoS genetics2018
The presence of rNTPs decreases the speed of mitochondrial DNA replication.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
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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
20 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- The low endoribonuclease activity and lack of rNMP preference of human mitochondrial topoisomerase 1 protect against ribonucleotide-dependent deletions.Nucleic acids research · 2025Article
- Article
- Light-strand bias and enriched zones of embedded ribonucleotides are associated with DNA replication and transcription in the human-mitochondrial genome.Nucleic acids research · 2024Article
- How RNA impacts DNA repair.DNA repair · 2023Review
- Enhanced mitochondrial G-quadruplex formation impedes replication fork progression leading to mtDNA loss in human cells.Nucleic acids research · 2023Article
- Rolling Circle Replication and Bypass of Damaged Nucleotides.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- Ribonucleotides embedded in template DNA impair mitochondrial RNA polymerase progression.Nucleic acids research · 2022Article
- Remdesivir triphosphate blocks DNA synthesis and increases exonucleolysis by the replicative mitochondrial DNA polymerase, Pol γ.Mitochondrion · 2021Article
- Etheno adducts: from tRNA modifications to DNA adducts and back to miscoding ribonucleotides.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- Mechanisms of damage tolerance and repair during DNA replication.Nucleic acids research · 2021Review
- A unique arginine cluster in PolDIP2 enhances nucleotide binding and DNA synthesis by PrimPol.Nucleic acids research · 2021Article
- Mitochondrial DNA Damage: Prevalence, Biological Consequence, and Emerging Pathways.Chemical research in toxicology · 2020Review
- Elimination of rNMPs from mitochondrial DNA has no effect on its stability.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Impact of 1,The Journal of biological chemistry · 2020Article
- One, No One, and One Hundred Thousand: The Many Forms of Ribonucleotides in DNA.International journal of molecular sciences · 2020Review
- Mitochondria in the signaling pathways that control longevity and health span.Ageing research reviews · 2019Review
- Human DNA polymerase η has reverse transcriptase activity in cellular environments.The Journal of biological chemistry · 2019Article
- Current perspectives on mechanisms of ribonucleotide incorporation and processing in mammalian DNA.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2019Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribonucleotides (rNMPs) are frequently incorporated during replication or repair by DNA polymerases and failure to remove them leads to instability of nuclear DNA (nDNA). Conversely, rNMPs appear to be relatively well-tolerated in mitochondrial DNA (mtDNA), although the mechanisms behind the tolerance remain unclear. We here show that the human mitochondrial DNA polymerase gamma (Pol γ) bypasses single rNMPs with an unprecedentedly high fidelity and efficiency. In addition, Pol γ exhibits a strikingly low frequency of rNMP incorporation, a property, which we find is independent of its exonuclease activity. However, the physiological levels of free rNTPs partially inhibit DNA synthesis by Pol γ and render the polymerase more sensitive to imbalanced dNTP pools. The characteristics of Pol γ reported here could have implications for forms of mtDNA depletion syndrome (MDS) that are associated with imbalanced cellular dNTP pools. Our results show that at the rNTP/dNTP ratios that are expected to prevail in such disease states, Pol γ enters a polymerase/exonuclease idling mode that leads to mtDNA replication stalling. This could ultimately lead to mtDNA depletion and, consequently, to mitochondrial disease phenotypes such as those observed in MDS.
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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.