ArticleNucleic acids research2020
Oxidative damage diminishes mitochondrial DNA polymerase replication fidelity.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 95 citations in OpenAlex.
- Oxidized mitochondrial DNA as a potential biomarker and mechanistic driver of autophagy-mitophagy dysregulation in pulmonary arterial hypertension: a narrative review.Molecular biology reports · 2026Review
- Shifting the Balance: Mitochondrial Heteroplasmy as a Driver of Cardiac Disease.Circulation research · 2026Review
- Review
- Pol γ possesses separate metal binding sites for polymerase and strand displacement functions.Nucleic acids research · 2026Article
- Mitochondria transplantation reduces intraocular pressure by improving mitochondrial function and remodeling trabecular meshwork.Journal of translational medicine · 2026Article
- Molecular and cellular processes connecting type 2 diabetes to Alzheimer's disease, focusing on oxidative stress, metabolic dysfunction, and neurodegeneration.Genetics and molecular biology · 2026Article
- Article
- Cell-free DNA in sepsis: from molecular insights to clinical management.Military Medical Research · 2025Review
- Brain somatic mutations in Alzheimer's disease: linking genetic mosaicism to neurodegeneration.Molecular neurodegeneration · 2025Review
- Mitochondria in oxidative stress, inflammation and aging: from mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.G3 (Bethesda, Md.) · 2025Article
- Aging through the lens of mitochondrial DNA mutations and inheritance paradoxes.Biogerontology · 2024Review
- The aging heart: exploring the role of Klotho in cardiac health/function.The journal of cardiovascular aging · 2024Article
- The Role of Non-Coding RNAs in Mitochondrial Dysfunction of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Cytoplasmic binding partners of the Integrator endonuclease INTS11 and its paralog CPSF73 are required for their nuclear function.Molecular cell · 2024Article
- Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.bioRxiv : the preprint server for biology · 2024Article
- Review
- CRISPR/Cas9-mediated base editors and their prospects for mitochondrial genome engineering.Gene therapy · 2024Review
- Single-strand mismatch and damage patterns revealed by single-molecule DNA sequencing.bioRxiv : the preprint server for biology · 2023Article
- Structural and Molecular Basis for Mitochondrial DNA Replication and Transcription in Health and Antiviral Drug Toxicity.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondrial DNA (mtDNA) resides in a high ROS environment and suffers more mutations than its nuclear counterpart. Increasing evidence suggests that mtDNA mutations are not the results of direct oxidative damage, rather are caused, at least in part, by DNA replication errors. To understand how the mtDNA replicase, Pol γ, can give rise to elevated mutations, we studied the effect of oxidation of Pol γ on replication errors. Pol γ is a high fidelity polymerase with polymerase (pol) and proofreading exonuclease (exo) activities. We show that Pol γ exo domain is far more sensitive to oxidation than pol; under oxidative conditions, exonuclease activity therefore declines more rapidly than polymerase. The oxidized Pol γ becomes editing-deficient, displaying a 20-fold elevated mutations than the unoxidized enzyme. Mass spectrometry analysis reveals that Pol γ exo domain is a hotspot for oxidation. The oxidized exo residues increase the net negative charge around the active site that should reduce the affinity to mismatched primer/template DNA. Our results suggest that the oxidative stress induced high mutation frequency on mtDNA can be indirectly caused by oxidation of the mitochondrial replicase.
Indexed as
Identifiers
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.