ArticleMolecular and cellular biology2008
Removal of oxidative DNA damage via FEN1-dependent long-patch base excision repair in human cell mitochondria.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.
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Who cites it
133 citing papers in PubMed, 204 citations in OpenAlex.
- Two distinct Okazaki fragment failure modes dominate mutagenesis in the absence of flap endonuclease 1.Nature communications · 2026Article
- Persistence of large mtDNA rearrangements linked to premature aging in Pol γ exonuclease-deficient mice.Nucleic acids research · 2026Article
- CypD Dependent mPTP Opening Is Crucial for Oxidized Mitochondrial DNA Release in Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deficiency ofZoological research · 2026Article
- Review
- Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.Nucleic acids research · 2025Article
- Mammalian DNA ligases; roles in maintaining genome integrity.Journal of molecular biology · 2024Review
- Maintenance of Flap Endonucleases for Long-Patch Base Excision DNA Repair in Mouse Muscle and Neuronal Cells Differentiated In Vitro.International journal of molecular sciences · 2023Article
- RNA G-Quadruplex within the 5'-UTR of FEN1 Regulates mRNA Stability under Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Article
- Human EXOG Possesses Strong AP Hydrolysis Activity: Implication on Mitochondrial DNA Base Excision Repair.Journal of the American Chemical Society · 2022Article
- Article
- Mitochondrial DNA Repair in Neurodegenerative Diseases and Ageing.International journal of molecular sciences · 2022Review
- In vitro reconstitution reveals a key role of human mitochondrial EXOG in RNA primer processing.Nucleic acids research · 2022Article
- Article
- The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ.Breast cancer research and treatment · 2021Article
- FEN1 is a prognostic biomarker for ER+ breast cancer and associated with tamoxifen resistance through the ERα/cyclin D1/Rb axis.Annals of translational medicine · 2021Article
- The Mitochondrial Response to DNA Damage.Frontiers in cell and developmental biology · 2021Review
- Polymerase γ efficiently replicates through many natural template barriers but stalls at the HSP1 quadruplex.The Journal of biological chemistry · 2020Article
- Strand Displacement Activity of PrimPol.International journal of molecular sciences · 2020Article
- The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System.Molecules (Basel, Switzerland) · 2020Review
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Repair of oxidative DNA damage in mitochondria was thought limited to short-patch base excision repair (SP-BER) replacing a single nucleotide. However, certain oxidative lesions cannot be processed by SP-BER. Here we report that 2-deoxyribonolactone (dL), a major type of oxidized abasic site, inhibits replication by mitochondrial DNA (mtDNA) polymerase gamma and interferes with SP-BER by covalently trapping polymerase gamma during attempted dL excision. However, repair of dL was detected in human mitochondrial extracts, and we show that this repair is via long-patch BER (LP-BER) dependent on flap endonuclease 1 (FEN1), not previously known to be present in mitochondria. FEN1 was retained in protease-treated mitochondria and detected in mitochondrial nucleoids that contain known mitochondrial replication and transcription proteins. Results of immunofluorescence and subcellular fractionation studies were also consistent with the presence of FEN1 in the mitochondria of intact cells. Immunodepletion experiments showed that the LP-BER activity of mitochondrial extracts was strongly diminished in parallel with the removal of FEN1, although some activity remained, suggesting the presence of an additional flap-removing enzyme. Biological evidence for a FEN1 role in repairing mitochondrial oxidative DNA damage was provided by RNA interference experiments, with the extent of damage greater and the recovery slower in FEN1-depleted cells than in control cells. The mitochondrial LP-BER pathway likely plays important roles in repairing dL lesions and other oxidative lesions and perhaps in normal mtDNA replication.
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Registered trials
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