ArticleNucleic acids research2016
DNA polymerase θ specializes in incorporating synthetic expanded-size (xDNA) nucleotides.
Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed, 23 citations in OpenAlex.
- The Evolutionary Potential of Chromoanagenesis.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Polθ: emerging synthetic lethal partner in homologous recombination-deficient tumors.Cancer gene therapy · 2024Review
- Melanoma-Derived DNA Polymerase Theta Variants Exhibit Altered DNA Polymerase Activity.Biochemistry · 2024Article
- Inhibitors against DNA Polymerase I Family of Enzymes: Novel Targets and Opportunities.Biology · 2024Review
- Promoter-independent synthesis of chemically modified RNA by human DNA polymerase θ variants.RNA (New York, N.Y.) · 2023Article
- Small Molecules Targeting DNA Polymerase Theta (POLθ) as Promising Synthetic Lethal Agents for Precision Cancer Therapy.Journal of medicinal chemistry · 2023Review
- Review
- Polθ reverse transcribes RNA and promotes RNA-templated DNA repair.Science advances · 2021Article
- Deciphering the H-Bonding Preference on Nucleoside Molecular Recognition through Model Copper(II) Compounds.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Review
- Enzymatic synthesis of random sequences of RNA and RNA analogues by DNA polymerase theta mutants for the generation of aptamer libraries.Nucleic acids research · 2018Article
- The helicase domain of Polθ counteracts RPA to promote alt-NHEJ.Nature structural & molecular biology · 2017Article
- Fluorescent nucleobases as tools for studying DNA and RNA.Nature chemistry · 2017Review
- NAngewandte Chemie (International ed. in English) · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
DNA polymerase θ (Polθ) is a unique A-family polymerase that is essential for alternative end-joining (alt-EJ) of double-strand breaks (DSBs) and performs translesion synthesis. Because Polθ is highly expressed in cancer cells, confers resistance to ionizing radiation and chemotherapy agents, and promotes the survival of homologous recombination (HR) deficient cells, it represents a promising new cancer drug target. As a result, identifying substrates that are selective for this enzyme is a priority. Here, we demonstrate that Polθ efficiently and selectively incorporates into DNA large benzo-expanded nucleotide analogs (dxAMP, dxGMP, dxTMP, dxAMP) which exhibit canonical base-pairing and enhanced base stacking. In contrast, functionally related Y-family translesion polymerases exhibit a severely reduced ability to incorporate dxNMPs, and all other human polymerases tested from the X, B and A families fail to incorporate them under the same conditions as Polθ. We further find that Polθ is inhibited after multiple dxGMP incorporation events, and that Polθ efficiency for dxGMP incorporation approaches that of native dGMP. These data demonstrate a unique function for Polθ in incorporating synthetic large-sized nucleotides and suggest the future possibility of the use of dxG nucleoside or related prodrug analogs as selective inhibitors of Polθ activity.
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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.