ArticleProceedings of the National Academy of Sciences of the United States of America2012
Structural basis of human DNA polymerase η-mediated chemoresistance to cisplatin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 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
103 citing papers in PubMed, 153 citations in OpenAlex.
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- smDeepFLUOR: single-molecule deep learning fluorescence classification.Nature communications · 2026Article
- Translesion polymerases and DNA-protein crosslink repair shapes the cellular response to formaldehyde-induced DNA damage in ssDNA.Nucleic acids research · 2025Article
- Human TLS DNA polymerase: saviors or threats under replication stress?Molecular and cellular biochemistry · 2025Review
- Insights into the DNA damage response and tumor drug resistance.Cancer biology & medicine · 2025Article
- Review
- Connecting dots between nucleotide biosynthesis and DNA lesion repair/bypass in cancer.Bioscience reports · 2024Review
- Protein Assemblies in Translesion Synthesis.Genes · 2024Review
- Cisplatin in the era of PARP inhibitors and immunotherapy.Pharmacology & therapeutics · 2024Review
- Novel insights into the role of translesion synthesis polymerase in DNA incorporation and bypass of 5-fluorouracil in colorectal cancer.Nucleic acids research · 2024Article
- RAD18 O-GlcNAcylation promotes translesion DNA synthesis and homologous recombination repair.Cell death & disease · 2024Article
- For the Better or for the Worse? The Effect of Manganese on the Activity of Eukaryotic DNA Polymerases.International journal of molecular sciences · 2023Review
- Repair and tolerance of DNA damage at the replication fork: A structural perspective.Current opinion in structural biology · 2023Review
- Nucleophosmin Plays a Role in Repairing DNA Damage and Is a Target for Cancer Treatment.Cancer research · 2023Review
- Identification of Three Human POLH Germline Variants Defective in Complementing the UV- and Cisplatin-Sensitivity of POLH-Deficient Cells.International journal of molecular sciences · 2023Article
- Structural basis of DNA polymerase θ mediated DNA end joining.Nucleic acids research · 2023Article
- Design of amino acid- and carbohydrate-based anticancer drugs to inhibit polymerase η.Scientific reports · 2022Article
- Predicting the Prognostic Value ofInternational journal of molecular sciences · 2022Article
- DNA polymerase η promotes nonhomologous end joining upon etoposide exposure dependent on the scaffolding protein Kap1.The Journal of biological chemistry · 2022Article
- Article
43 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 4 countries.
Funding
Abstract
Cisplatin (cis-diamminedichloroplatinum) and related compounds cause DNA damage and are widely used as anticancer agents. Chemoresistance to cisplatin treatment is due in part to translesion synthesis by human DNA polymerase η (hPol η). Here, we report crystal structures of hPol η complexed with intrastrand cisplatin-1,2-cross-linked DNA, representing four consecutive steps in translesion synthesis. In contrast to the generally enlarged and nondiscriminating active site of Y-family polymerases like Dpo4, Pol η is specialized for efficient bypass of UV-cross-linked pyrimidine dimers. Human Pol η differs from the yeast homolog in its binding of DNA template. To incorporate deoxycytidine opposite cisplatin-cross-linked guanines, hPol η undergoes a specific backbone rearrangement to accommodate the larger base dimer and minimizes the DNA distortion around the lesion. Our structural analyses show why Pol η is inefficient at extending primers after cisplatin lesions, which necessitates a second translesion DNA polymerase to complete bypass in vivo. A hydrophobic pocket near the primer-binding site in human Pol η is identified as a potential drug target for inhibiting translesion synthesis and, thereby, reducing chemoresistance.
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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.