ArticleCell reports2021
BRCA2 deficiency reveals that oxidative stress impairs RNaseH1 function to cripple mitochondrial DNA maintenance.
Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Ataxia and oculomotor apraxia caused by a large-scale deletion in the senataxin gene.Journal of applied genetics · 2026Article
- The Prognostic Nutritional Index as a Lifeline for Cardiovascular Health in Individuals With Insomnia: A Prospective Cohort Study.Health science reports · 2026Article
- HELZ is a RNA-DNA helicase that resolves R loops to facilitate homologous recombination repair.Nature communications · 2026Article
- Landscape of plastid DNA breaks in Arabidopsis during development and environmental stimulus.The Plant cell · 2026Article
- Exploring the Mechanisms of Total Saponins of Black Ginseng and Ginsenoside Rg3 Against Doxorubicin-Induced Cardiotoxicity.Food science & nutrition · 2026Article
- Revisiting osteoarthritis pathogenesis through the lens of cGAS-STING: Mitochondrial damage, pyroptosis, and inflammatory cascades.Journal of orthopaedic translation · 2026Review
- Identification of Mitochondrial-Related Signature in Allergic Rhinitis: Novel Insights from Bioinformatics and Machine Learning.Journal of inflammation research · 2026Article
- Pathogenic role of mitochondrial DNA mutations in heart failure: clinical features, mechanisms, and therapeutic prospects.Frontiers in cardiovascular medicine · 2026Review
- Atypical R-loops in cancer: decoding molecular chaos for therapeutic gain.Journal of translational medicine · 2025Review
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- BRCA2 C-terminal clamp restructures RAD51 dimers to bind B-DNA for replication fork stability.Molecular cell · 2025Article
- Elevated reactive oxygen species can drive the alternative lengthening of telomeres pathway in ATRX-null cancers.Nucleic acids research · 2025Article
- Black seed oil reverses chronic antibiotic-mediated depression and social behaviour deficits via modulation of hypothalamic mitochondrial-dependent markers and insulin expression.IBRO neuroscience reports · 2024Article
- Hypoxia-induced transcriptional stress is mediated by ROS-induced R-loops.Nucleic acids research · 2023Article
- The RNA m5C modification in R-loops as an off switch of Alt-NHEJ.Nature communications · 2023Article
- Ribonucleotide and R-Loop Damage in Plastid DNA and Mitochondrial DNA during Maize Development.Plants (Basel, Switzerland) · 2023Article
- The Tumor Suppressor BRCA1/2, Cancer Susceptibility and Genome Instability in Gynecological and Mammary Cancers.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- Human PNPase causes RNA stabilization and accumulation of R-loops in the Escherichia coli model system.Scientific reports · 2023Article
- Senataxin and R-loops homeostasis: multifaced implications in carcinogenesis.Cell death discovery · 2023Review
- The Role of Genetic Mutations in Mitochondrial-Driven Cancer Growth in Selected Tumors: Breast and Gynecological Malignancies.Life (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Oxidative stress is a ubiquitous cellular challenge implicated in aging, neurodegeneration, and cancer. By studying pathogenic mutations in the tumor suppressor BRCA2, we identify a general mechanism by which oxidative stress restricts mitochondrial (mt)DNA replication. BRCA2 inactivation induces R-loop accumulation in the mtDNA regulatory region and diminishes mtDNA replication initiation. In BRCA2-deficient cells, intracellular reactive oxygen species (ROS) are elevated, and ROS scavengers suppress the mtDNA defects. Conversely, wild-type cells exposed to oxidative stress by pharmacologic or genetic manipulation phenocopy these defects. Mechanistically, we find that 8-oxoguanine accumulation in mtDNA caused by oxidative stress suffices to impair recruitment of the mitochondrial enzyme RNaseH1 to sites of R-loop accrual, restricting mtDNA replication initiation. Thus, oxidative stress impairs RNaseH1 function to cripple mtDNA maintenance. Our findings highlight a molecular mechanism that links oxidative stress to mitochondrial dysfunction and is elicited by the inactivation of genes implicated in neurodegeneration and cancer.
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Registered trials
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