ArticleNucleic acids research2013
A small molecule directly inhibits the p53 transactivation domain from binding to replication protein A.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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
23 citing papers in PubMed, 35 citations in OpenAlex.
- Targeting DNA repair mechanisms in cancer therapy: the role of small molecule DNA repair inhibitors.NAR cancer · 2025Review
- Targeting DNA damage sensors for cancer therapy.DNA repair · 2025Review
- Review
- The effect of replication protein A inhibition and post-translational modification on ATR kinase signaling.Scientific reports · 2024Article
- The Effect of Replication Protein A Inhibition and Post-Translational Modification on ATR Kinase Signaling.Research square · 2024Article
- Article
- Chemical Inhibition of RPA by HAMNO Alters Cell Cycle Dynamics by Impeding DNA Replication and G2-to-M Transition but Has Little Effect on the Radiation-Induced DNA Damage Response.International journal of molecular sciences · 2023Article
- Recent Advances in the Development of Non-PIKKs Targeting Small Molecule Inhibitors of DNA Double-Strand Break Repair.Frontiers in oncology · 2022Review
- OB-Folds and Genome Maintenance: Targeting Protein-DNA Interactions for Cancer Therapy.Cancers · 2021Review
- Structure-Guided Optimization of Replication Protein A (RPA)-DNA Interaction Inhibitors.ACS medicinal chemistry letters · 2020Article
- Targeting repair pathways with small molecules increases precise genome editing in pluripotent stem cells.Nature communications · 2018Article
- Recent advancements in the discovery of protein-protein interaction inhibitors of replication protein A.MedChemComm · 2017Review
- Identification of inhibitors for single-stranded DNA-binding proteins in eubacteria.The Journal of antimicrobial chemotherapy · 2016Article
- Force regulated dynamics of RPA on a DNA fork.Nucleic acids research · 2016Article
- Improvements in GROMACS plugin for PyMOL including implicit solvent simulations and displaying results of PCA analysis.Journal of molecular modeling · 2016Article
- Identification and Optimization of Anthranilic Acid Based Inhibitors of Replication Protein A.ChemMedChem · 2016Article
- DNA repair targeted therapy: The past or future of cancer treatment?Pharmacology & therapeutics · 2016Review
- Single-molecule imaging reveals the mechanism of Exo1 regulation by single-stranded DNA binding proteins.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- RPA inhibition increases replication stress and suppresses tumor growth.Cancer research · 2014Article
- ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency.Cancer research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Replication protein A (RPA), essential for DNA replication, repair and DNA damage signalling, possesses six ssDNA-binding domains (DBDs), including DBD-F on the N-terminus of the largest subunit, RPA70. This domain functions as a binding site for p53 and other DNA damage and repair proteins that contain amphipathic alpha helical domains. Here, we demonstrate direct binding of both ssDNA and the transactivation domain 2 of p53 (p53TAD2) to DBD-F, as well as DBD-F-directed dsDNA strand separation by RPA, all of which are inhibited by fumaropimaric acid (FPA). FPA binds directly to RPA, resulting in a conformational shift as determined through quenching of intrinsic tryptophan fluorescence in full length RPA. Structural analogues of FPA provide insight on chemical properties that are required for inhibition. Finally, we confirm the inability of RPA possessing R41E and R43E mutations to bind to p53, destabilize dsDNA and quench tryptophan fluorescence by FPA, suggesting that protein binding, DNA modulation and inhibitor binding all occur within the same site on DBD-F. The disruption of p53-RPA interactions by FPA may disturb the regulatory functions of p53 and RPA, thereby inhibiting cellular pathways that control the cell cycle and maintain the integrity of the human genome.
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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.