ArticlePloS one2012
A comprehensive strategy to discover inhibitors of the translesion synthesis DNA polymerase κ.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 36 citations in OpenAlex.
- Utilization of natural products in diverse pathogeneses of diseases associated with single or double DNA strand damage repair.Chinese medicine · 2025Review
- Human translesion DNA polymerases ι and κ mediate tolerance to temozolomide in MGMT-deficient glioblastoma cells.DNA repair · 2024Article
- Alterations in Molecular Profiles Affecting Glioblastoma Resistance to Radiochemotherapy: Where Does the Good Go?Cancers · 2022Review
- Targeting protein-protein interactions in the DNA damage response pathways for cancer chemotherapy.RSC chemical biology · 2021Review
- Translesion synthesis inhibitors as a new class of cancer chemotherapeutics.Expert opinion on investigational drugs · 2021Review
- DNA Damage Tolerance Pathways in Human Cells: A Potential Therapeutic Target.Frontiers in oncology · 2021Review
- Review
- Regulation of the error-prone DNA polymerase Polκ by oncogenic signaling and its contribution to drug resistance.Science signaling · 2020Article
- DNA damage tolerance in stem cells, ageing, mutagenesis, disease and cancer therapy.Nucleic acids research · 2019Review
- Mammalian DNA Polymerase Kappa Activity and Specificity.Molecules (Basel, Switzerland) · 2019Review
- Article
- Inhibition of Human DNA Polymerases Eta and Kappa by Indole-Derived Molecules Occurs through Distinct Mechanisms.ACS chemical biology · 2019Article
- The Rev1-Polζ translesion synthesis mutasome: Structure, interactions and inhibition.The Enzymes · 2019Review
- A Small-Molecule Inhibitor of Human DNA Polymerase η Potentiates the Effects of Cisplatin in Tumor Cells.Biochemistry · 2018Article
- Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities.Chemical research in toxicology · 2017Review
- Inhibition of mutagenic translesion synthesis: A possible strategy for improving chemotherapy?PLoS genetics · 2017Review
- Cell-free Xenopus egg extracts for studying DNA damage response pathways.The International journal of developmental biology · 2016Review
- Ubiquitination events that regulate recombination of immunoglobulin Loci gene segments.Frontiers in immunology · 2014Review
- N-Aroyl indole thiobarbituric acids as inhibitors of DNA repair and replication stress response polymerases.ACS chemical biology · 2013Article
- Leukotriene biosynthesis inhibitor MK886 impedes DNA polymerase activity.Chemical research in toxicology · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Human DNA polymerase kappa (pol κ) is a translesion synthesis (TLS) polymerase that catalyzes TLS past various minor groove lesions including N(2)-dG linked acrolein- and polycyclic aromatic hydrocarbon-derived adducts, as well as N(2)-dG DNA-DNA interstrand cross-links introduced by the chemotherapeutic agent mitomycin C. It also processes ultraviolet light-induced DNA lesions. Since pol κ TLS activity can reduce the cellular toxicity of chemotherapeutic agents and since gliomas overexpress pol κ, small molecule library screens targeting pol κ were conducted to initiate the first step in the development of new adjunct cancer therapeutics. A high-throughput, fluorescence-based DNA strand displacement assay was utilized to screen ∼16,000 bioactive compounds, and the 60 top hits were validated by primer extension assays using non-damaged DNAs. Candesartan cilexetil, manoalide, and MK-886 were selected as proof-of-principle compounds and further characterized for their specificity toward pol κ by primer extension assays using DNAs containing a site-specific acrolein-derived, ring-opened reduced form of γ-HOPdG. Furthermore, candesartan cilexetil could enhance ultraviolet light-induced cytotoxicity in xeroderma pigmentosum variant cells, suggesting its inhibitory effect against intracellular pol κ. In summary, this investigation represents the first high-throughput screening designed to identify inhibitors of pol κ, with the characterization of biochemical and biologically relevant endpoints as a consequence of pol κ inhibition. These approaches lay the foundation for the future discovery of compounds that can be applied to combination chemotherapy.
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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.