ArticleProceedings of the National Academy of Sciences of the United States of America2014
Structural and mechanistic studies of polymerase η bypass of phenanthriplatin DNA damage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Reimagining Pt(II) Anticancer Agents: The Role of Ferrocene in Monofunctional Chemotherapeutic Compounds.Inorganic chemistry · 2025Article
- Review
- The Influence of the Auxiliary Ligand in Monofunctional Pt(II) Anticancer Complexes on the DNA Backbone.International journal of molecular sciences · 2024Article
- Click-Capable Phenanthriplatin Derivatives as Tools to Study Pt(II)-Induced Nucleolar Stress.ACS chemical biology · 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
- In crystallo observation of active site dynamics and transient metal ion binding within DNA polymerases.Structural dynamics (Melville, N.Y.) · 2023Article
- In crystallo observation of three metal ion promoted DNA polymerase misincorporation.Nature communications · 2022Article
- Article
- Intercalation Ability of Novel Monofunctional Platinum Anticancer Drugs: A Key Step in Their Biological Action.Journal of chemical information and modeling · 2021Article
- Monofunctional Platinum(II) Anticancer Agents.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Translesion synthesis of the major nitrogen mustard-induced DNA lesion by human DNA polymerase η.The Biochemical journal · 2020Article
- Tuning the Reactivity and Bonding Properties of Metal Square-Planar Complexes by the Substitution(s) on the Trans-Coordinated Pyridine Ring.ACS omega · 2020Article
- New Findings in the Signaling Pathways ofACS omega · 2019Article
- Bypass of the Major Alkylative DNA Lesion by Human DNA Polymerase η.Molecules (Basel, Switzerland) · 2019Article
- Platinum-induced peripheral neurotoxicity: From pathogenesis to treatment.Journal of the peripheral nervous system : JPNS · 2019Review
- Monofunctional platinum(II) compounds and nucleolar stress: is phenanthriplatin unique?Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- Mutagenic Replication of the Major Oxidative Adenine Lesion 7,8-Dihydro-8-oxoadenine by Human DNA Polymerases.Journal of the American Chemical Society · 2019Article
- DNA Intercalation Facilitates Efficient DNA-Targeted Covalent Binding of Phenanthriplatin.Journal of the American Chemical Society · 2019Article
- Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase η at atomic resolution.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Platinum drugs are a mainstay of anticancer chemotherapy. Nevertheless, tumors often display inherent or acquired resistance to platinum-based treatments, prompting the search for new compounds that do not exhibit cross-resistance with current therapies. Phenanthriplatin, cis-diamminephenanthridinechloroplatinum(II), is a potent monofunctional platinum complex that displays a spectrum of activity distinct from those of the clinically approved platinum drugs. Inhibition of RNA polymerases by phenanthriplatin lesions has been implicated in its mechanism of action. The present study evaluates the ability of phenanthriplatin lesions to inhibit DNA replication, a function disrupted by traditional platinum drugs. Phenanthriplatin lesions effectively inhibit DNA polymerases ν, ζ, and κ and the Klenow fragment. In contrast to results obtained with DNA damaged by cisplatin, all of these polymerases were capable of inserting a base opposite a phenanthriplatin lesion, but only Pol η, an enzyme efficient in translesion synthesis, was able to fully bypass the adduct, albeit with low efficiency. X-ray structural characterization of Pol η complexed with site-specifically platinated DNA at both the insertion and +1 extension steps reveals that phenanthriplatin on DNA interacts with and inhibits Pol η in a manner distinct from that of cisplatin-DNA adducts. Unlike cisplatin and oxaliplatin, the efficacies of which are influenced by Pol η expression, phenanthriplatin is highly toxic to both Pol η+ and Pol η- cells. Given that increased expression of Pol η is a known mechanism by which cells resist cisplatin treatment, phenanthriplatin may be valuable in the treatment of cancers that are, or can easily become, resistant to cisplatin.
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