ArticleAntimicrobial agents and chemotherapy2016
Insights into the Molecular Mechanism of Polymerization and Nucleoside Reverse Transcriptase Inhibitor Incorporation by Human PrimPol.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- 3'dNTP Binding Is Modulated during Primer Synthesis and Translesion by Human PrimPol.International journal of molecular sciences · 2023Article
- Exploring ABOBEC3A and APOBEC3B substrate specificity and their role in HPV positive head and neck cancer.iScience · 2022Article
- Mitochondrial DNA Instability in Mammalian Cells.Antioxidants & redox signaling · 2022Review
- PrimPol: A Breakthrough among DNA Replication Enzymes and a Potential New Target for Cancer Therapy.Biomolecules · 2022Review
- Article
- Strand Displacement Activity of PrimPol.International journal of molecular sciences · 2020Article
- Mechanisms of direct replication restart at stressed replisomes.DNA repair · 2020Review
- A Clinical Metabolite of Azidothymidine Inhibits Experimental Choroidal Neovascularization and Retinal Pigmented Epithelium Degeneration.Investigative ophthalmology & visual science · 2020Article
- Identifying the role of PrimPol in TDF-induced toxicity and implications of its loss of function mutation in an HIV+ patient.Scientific reports · 2020Article
- Divalent Cations Alter the Rate-Limiting Step of PrimPol-Catalyzed DNA Elongation.Journal of molecular biology · 2019Article
- Activity and fidelity of human DNA polymerase α depend on primer structure.The Journal of biological chemistry · 2018Article
- DNA Damage Tolerance by Eukaryotic DNA Polymerase and Primase PrimPol.International journal of molecular sciences · 2017Review
- Mitochondrial DNA replication: a PrimPol perspective.Biochemical Society transactions · 2017Review
- Optimization of the expression, purification and polymerase activity reaction conditions of recombinant human PrimPol.PloS one · 2017Article
- Off-Target Effects of Drugs that Disrupt Human Mitochondrial DNA Maintenance.Frontiers in molecular biosciences · 2017Review
- Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol.DNA repair · 2017Article
- DNA polymerases in the mitochondria: A critical review of the evidence.Frontiers in bioscience (Landmark edition) · 2017Review
- Oxidative DNA damage stalls the human mitochondrial replisome.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Human PrimPol is a newly identified DNA and RNA primase-polymerase of the archaeo-eukaryotic primase (AEP) superfamily and only the second known polymerase in the mitochondria. Mechanistic studies have shown that interactions of the primary mitochondrial DNA polymerase γ (mtDNA Pol γ) with nucleoside reverse transcriptase inhibitors (NRTIs), key components in treating HIV infection, are a major source of NRTI-associated toxicity. Understanding the interactions of host polymerases with antiviral and anticancer nucleoside analog therapies is critical for preventing life-threatening adverse events, particularly in AIDS patients who undergo lifelong treatment. Since PrimPol has only recently been discovered, the molecular mechanism of polymerization and incorporation of natural nucleotide and NRTI substrates, crucial for assessing the potential for PrimPol-mediated NRTI-associated toxicity, has not been explored. We report for the first time a transient-kinetic analysis of polymerization for each nucleotide and NRTI substrate as catalyzed by PrimPol. These studies reveal that nucleotide selectivity limits chemical catalysis while the release of the elongated DNA product is the overall rate-limiting step. Remarkably, PrimPol incorporates four of the eight FDA-approved antiviral NRTIs with a kinetic profile distinct from that of mtDNA Pol γ that may manifest in 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.