ArticleThe EMBO journal2015
Structural basis for processivity and antiviral drug toxicity in human mitochondrial DNA replicase.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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
49 citing papers in PubMed, 65 citations in OpenAlex.
- Molecular and structural basis for replication initiation and strand separation by human mitochondrial DNA polymerase γ.Nucleic acids research · 2026Article
- Structural and single-molecule insights into the core human mitochondrial DNA replisome.The Biochemical journal · 2026Review
- Pol γ possesses separate metal binding sites for polymerase and strand displacement functions.Nucleic acids research · 2026Article
- Higher-order structural organization of mitochondrial metabolism.The Journal of biological chemistry · 2026Review
- Mitochondrial DNA Replication and Disease: A Historical Perspective on Molecular Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Comparison of Magnesium and Manganese Ions on the Structural and Catalytic Properties of Human DNA Polymerase Gamma.Journal of chemical theory and computation · 2025Article
- A steric gate prevents mutagenic dATP incorporation opposite 8-oxo-deoxyguanosine in mitochondrial DNA polymerases.The FEBS journal · 2025Article
- Article
- Modelling POLG mutations in mice unravels a critical role of POLγΒ in regulating phenotypic severity.Nature communications · 2025Article
- Structural basis for intrinsic strand displacement activity of mitochondrial DNA polymerase.Nature communications · 2025Article
- Mitochondrial exonuclease EXOG supports DNA integrity by the removal of single-stranded DNA flaps.Nucleic acids research · 2025Article
- Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase.Journal of molecular biology · 2024Article
- Deregulation of mitochondrial gene expression in cancer: mechanisms and therapeutic opportunities.British journal of cancer · 2024Review
- Structures of the mitochondrial single-stranded DNA binding protein with DNA and DNA polymerase γ.Nucleic acids research · 2024Article
- Structural basis for substrate binding and selection by human mitochondrial RNA polymerase.Nature communications · 2024Article
- Coordinated DNA polymerization by Polγ and the region of LonP1 regulated proteolysis.Nucleic acids research · 2024Article
- An interaction network in the polymerase active site is a prerequisite for Watson-Crick base pairing in Pol γ.Science advances · 2024Article
- Structural basis for DNA proofreading.Nature communications · 2023Article
- Structure-specific roles for PolG2-DNA complexes in maintenance and replication of mitochondrial DNA.Nucleic acids research · 2023Article
- Polγ coordinates DNA synthesis and proofreading to ensure mitochondrial genome integrity.Nature structural & molecular biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The human DNA polymerase gamma (Pol γ) is responsible for DNA replication in mitochondria. Pol γ is particularly susceptible to inhibition by dideoxynucleoside-based inhibitors designed to fight viral infection. Here, we report crystal structures of the replicating Pol γ-DNA complex bound to either substrate or zalcitabine, an inhibitor used for HIV reverse transcriptase. The structures reveal that zalcitabine binds to the Pol γ active site almost identically to the substrate dCTP, providing a structural basis for Pol γ-mediated drug toxicity. When compared to the apo form, Pol γ undergoes intra- and inter-subunit conformational changes upon formation of the ternary complex with primer/template DNA and substrate. We also find that the accessory subunit Pol γB, which lacks intrinsic enzymatic activity and does not contact the primer/template DNA directly, serves as an allosteric regulator of holoenzyme activities. The structures presented here suggest a mechanism for processivity of the holoenzyme and provide a model for understanding the deleterious effects of Pol γ mutations in human disease. Crystal structures of the mitochondrial DNA polymerase, Pol γ, in complex with substrate or antiviral inhibitor zalcitabine provide a basis for understanding Pol γ-mediated drug toxicity.
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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.