ArticleMolecular pharmacology2012
DNA polymerase ζ is a major determinant of resistance to platinum-based chemotherapeutic agents.
Article in Molecular pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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
31 citing papers in PubMed, 57 citations in OpenAlex.
- REV1‑targeting inhibitor JH‑RE‑06 induces ferroptosis via NCOA4‑mediated ferritinophagy in colorectal cancer cells.Oncology reports · 2025Article
- Cytotoxicity and Binding to DNA, Lysozyme, Ribonuclease A, and Human Serum Albumin of the Diiodido Analog of Picoplatin.Inorganic chemistry · 2025Article
- Understanding microRNA-Mediated Chemoresistance in Colorectal Cancer Treatment.International journal of molecular sciences · 2025Review
- Proteomics and Bioinformatics Identify Drug-Resistant-Related Genes with Prognostic Potential in Cholangiocarcinoma.Biomolecules · 2024Article
- Article
- Translesion activity of PrimPol on DNA with cisplatin and DNA-protein cross-links.Scientific reports · 2021Article
- Oxaliplatin promotes siMAD2L2‑induced apoptosis in colon cancer cells.Molecular medicine reports · 2021Article
- Implications of inhibition of Rev1 interaction with Y family DNA polymerases for cisplatin chemotherapy.Genes & development · 2021Article
- Targeting REV7 effectively reverses 5-FU and oxaliplatin resistance in colorectal cancer.Cancer cell international · 2020Article
- A PolH Transcript with a Short 3'UTR Enhances PolH Expression and Mediates Cisplatin Resistance.Cancer research · 2019Article
- ATR mediates cisplatin resistance in 3D-cultured breast cancer cells via translesion DNA synthesis modulation.Cell death & disease · 2019Article
- Article
- Translesion Synthesis in Plants: Ultraviolet Resistance and Beyond.Frontiers in plant science · 2019Review
- Co-inhibition of Pol η and ATR sensitizes cisplatin-resistant non-small cell lung cancer cells to cisplatin by impeding DNA damage repair.Acta pharmacologica Sinica · 2018Article
- Small-molecules that bind to the ubiquitin-binding motif of REV1 inhibit REV1 interaction with K164-monoubiquitinated PCNA and suppress DNA damage tolerance.Bioorganic & medicinal chemistry · 2018Article
- MicroRNA-340 inhibits the proliferation and promotes the apoptosis of colon cancer cells by modulating REV3L.Oncotarget · 2018Article
- Family A and B DNA Polymerases in Cancer: Opportunities for Therapeutic Interventions.Biology · 2018Review
- Article
- Co-inhibition of pol θ and HR genes efficiently synergize with cisplatin to suppress cisplatin-resistant lung cancer cells survival.Oncotarget · 2016Article
- The Polymerase Activity of Mammalian DNA Pol ζ Is Specifically Required for Cell and Embryonic Viability.PLoS genetics · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Oxaliplatin, satraplatin, and picoplatin are cisplatin analogs that interact with DNA forming intrastrand and interstrand DNA cross-links (ICLs). Replicative bypass of cisplatin DNA adducts requires the cooperative actions of at least three translesion DNA synthesis (TLS) polymerases: Polη, REV1, and Polζ. Because oxaliplatin, satraplatin, and picoplatin contain bulkier chemical groups attached to the platinum core compared with cisplatin, we hypothesized that these chemical additions may impede replicative bypass by TLS polymerases and reduce tolerance to platinum-containing adducts. We examined multiple responses of cancer cells to oxaliplatin, satraplatin, or picoplatin treatment under conditions where expression of a TLS polymerase was limited. Our studies revealed that, although Polη contributes to the tolerance of cisplatin adducts, it plays a lesser role in promoting replication through oxaliplatin, satraplatin, and picoplatin adducts. REV1 and Polζ were necessary for tolerance to all four platinum analogs and prevention of hyperactivation of the DNA damage response after treatment. In addition, REV1 and Polζ were important for the resolution of DNA double-stranded breaks created during replication-associated repair of platinum-containing ICLs. Consistent with ICLs being the predominant cytotoxic lesion, depletion of REV1 or Polζ rendered two different model cell systems extremely sensitive to all four drugs, whereas Polη depletion had little effect. Together, our data suggest that REV1 and Polζ are critical for promoting resistance to all four clinically relevant platinum-based drugs by promoting both translesion DNA synthesis and DNA repair.
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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.