ArticleScience advances2017
Mitochondrial protein-linked DNA breaks perturb mitochondrial gene transcription and trigger free radical-induced DNA damage.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- CanInternational journal of molecular sciences · 2026Article
- Stiffness-dependent alveolar type II cell senescence in idiopathic pulmonary fibrosis.Cell communication and signaling : CCS · 2026Article
- Transcriptomic Analysis of TDP1-Knockout HEK293A Cells Treated with the TDP1 Inhibitor (Usnic Acid Derivative).International journal of molecular sciences · 2025Article
- Joining of DNA breaks- interplay between DNA ligases and poly (ADP-ribose) polymerases.DNA repair · 2025Review
- Insights into Nitrogen-Associated Protein 50 (NAP50) as a Tyrosyl-DNA Phosphodiesterase in Dinoflagellates.Microorganisms · 2024Article
- From the TOP: Formation, recognition and resolution of topoisomerase DNA protein crosslinks.DNA repair · 2024Review
- Oxidation balance scores are positively associated with the occurrence and severity of myopia in adults: results from the National Health and Nutrition Examination Survey 2007-2008.Molecular vision · 2024Article
- Role of Natural Antioxidants in Cancer.Cancer treatment and research · 2024Review
- Topically applied pH-responsive nanogels for alkyl radical-based therapy against psoriasiform hyperplasia.Drug delivery · 2023Article
- Research progress in mitochondrial gene editing technology.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2023Article
- The Role of Poly(ADP-ribose) Polymerase 1 in Nuclear and Mitochondrial Base Excision Repair.Biomolecules · 2023Review
- Antimicrobial peptide moricin induces ROS mediated caspase-dependent apoptosis in human triple-negative breast cancer via suppression of notch pathway.Cancer cell international · 2023Article
- Rapid profiling of DNA replication dynamics using mass spectrometry-based analysis of nascent DNA.The Journal of cell biology · 2023Article
- Ultra-small polydopamine nanomedicine-enabled antioxidation against senescence.Materials today. Bio · 2023Article
- Human topoisomerases and their roles in genome stability and organization.Nature reviews. Molecular cell biology · 2022Review
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- Antioxidant Therapy in Oxidative Stress-Induced Neurodegenerative Diseases: Role of Nanoparticle-Based Drug Delivery Systems in Clinical Translation.Antioxidants (Basel, Switzerland) · 2022Review
- Synthesis of Methoxy-, Methylenedioxy-, Hydroxy-, and Halo-Substituted Benzophenanthridinone Derivatives as DNA Topoisomerase IB (TOP1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1) Inhibitors and Their Biological Activity for Drug-Resistant Cancer.Journal of medicinal chemistry · 2021Article
- VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics.Nature communications · 2021Article
- Tdp1 protects from topoisomerase 1-mediated chromosomal breaks in adult zebrafish but is dispensable during larval development.Science advances · 2021Article
Corrections and comments
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Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
Breakage of one strand of DNA is the most common form of DNA damage. Most damaged DNA termini require end-processing in preparation for ligation. The importance of this step is highlighted by the association of defects in the 3'-end processing enzyme tyrosyl DNA phosphodiesterase 1 (TDP1) and neurodegeneration and by the cytotoxic induction of protein-linked DNA breaks (PDBs) and oxidized nucleic acid intermediates during chemotherapy and radiotherapy. Although much is known about the repair of PDBs in the nucleus, little is known about this process in the mitochondria. We reveal that TDP1 resolves mitochondrial PDBs (mtPDBs), thereby promoting mitochondrial gene transcription. Overexpression of a toxic form of mitochondrial topoisomerase I (TOP1mt*), which generates excessive mtPDBs, results in a TDP1-dependent compensatory up-regulation of mitochondrial gene transcription. In the absence of TDP1, the imbalance in transcription of mitochondrial- and nuclear-encoded electron transport chain (ETC) subunits results in misassembly of ETC complex III. Bioenergetics profiling further reveals that TDP1 promotes oxidative phosphorylation under both basal and high energy demands. It is known that mitochondrial dysfunction results in free radical leakage and nuclear DNA damage; however, the detection of intermediates of radical damage to DNA is yet to be shown. Consequently, we report an increased accumulation of carbon-centered radicals in cells lacking TDP1, using electron spin resonance spectroscopy. Overexpression of the antioxidant enzyme superoxide dismutase 1 (SOD1) reduces carbon-centered adducts and protects TDP1-deficient cells from oxidative stress. Conversely, overexpression of the amyotrophic lateral sclerosis-associated mutant SOD1
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