ArticleCancer research2020
Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Cholesterol and Its Derivatives: Multifaceted Players in Breast Cancer Progression.Frontiers in oncology · 2022Pooled it
- Fuzuloparib enhances radiosensitivity of gain-of-function mutant p53 R273H NSCLC by promoting SLC7A11/GSH/GPX4 axis mediated ferroptosis.NPJ precision oncology · 2026Article
- Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis.bioRxiv : the preprint server for biology · 2026Article
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- Ubiquitination of Oncogenic Mutant p53 via Attenuation of Ribosome Biogenesis Machinery Effectively Inhibits Pancreatic Tumor Growth.Molecular cancer therapeutics · 2026Article
- Effects of N361 Glycosylation on Epidermal Growth Factor Receptor Biological Function.Cancers · 2026Article
- Discovery of the PARP1 Inhibitors from Natural Compounds Using Structure-Based Virtual Screening and Bioactivity Evaluation.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026Article
- Mutant p53 variants differentially impact replication initiation and activate cGAS-STING to affect immune checkpoint inhibition.Communications biology · 2025Article
- Poly(ADP-ribose) polymerase-1 in breast cancers: expression level and its association in various molecular subtypes with a focus in Africa.Discover oncology · 2025Review
- Topoisomerase I Inhibition in ETV4-overexpressed Non-Small Cell Lung Cancer Promotes Replication and Transcription Mediated R-Loop Accumulation and DNA Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A base editing platform for the correction of cancer driver mutations unmasks conserved p53 transcription programs.Genome biology · 2025Article
- A cancer persistent DNA repair circuit driven by MDM2, MDM4 (MDMX), and mutant p53 for recruitment of MDC1 and 53BP1 on chromatin.Nucleic acids research · 2025Article
- Evaluating Biocompatibility: From Classical Techniques to State-of-the-Art Functional Proteomics.Nanomaterials (Basel, Switzerland) · 2025Review
- Article
- The Role of p53 Mutations in Early and Late Response to Mitotic Aberrations.Biomolecules · 2025Review
- MYC is Sufficient to Generate Mid-Life High-Grade Serous Ovarian and Uterine Serous Carcinomas in a p53-R270H Mouse Model.Cancer research communications · 2024Article
- A Theoretical Study of the Interaction of PARP-1 with Natural and Synthetic Inhibitors: Advances in the Therapy of Triple-Negative Breast Cancer.Current issues in molecular biology · 2024Article
- Genome-wide CRISPR screens identify novel regulators of wild-type and mutant p53 stability.Molecular systems biology · 2024Article
- Effective Radiosensitization of HNSCC Cell Lines by DNA-PKcs Inhibitor AZD7648 and PARP Inhibitors Talazoparib and Niraparib.International journal of molecular sciences · 2024Article
- Patient-derived tumor organoids with p53 mutations, and not wild-type p53, are sensitive to synergistic combination PARP inhibitor treatment.Cancer letters · 2024Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Over 80% of triple-negative breast cancers (TNBC) express mutant p53 (mtp53) and some contain oncogenic gain-of-function (GOF) p53. We previously reported that GOF mtp53 R273H upregulates the chromatin association of mini chromosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis. In this study, we dissected the function and association between mtp53 and PARP using a number of different cell lines, patient-derived xenografts (PDX), tissue microarrays (TMA), and The Cancer Genome Atlas (TCGA) database. Endogenous mtp53 R273H and exogenously expressed R273H and R248W bound to nascent 5-ethynyl-2´-deoxyuridine-labeled replicating DNA. Increased mtp53 R273H enhanced the association of mtp53 and PARP on replicating DNA. Blocking poly-ADP-ribose gylcohydrolase also enhanced this association. Moreover, mtp53 R273H expression enhanced overall MCM2 levels, promoted cell proliferation, and improved the synergistic cytotoxicity of treatment with the alkylating agent temozolomide in combination with the PARP inhibitor (PARPi) talazoparib. Staining of p53 and PARP1 in breast cancer TMAs and comparison with the TCGA database indicated a higher double-positive signal in basal-like breast cancer than in luminal A or luminal B subtypes. Higher PARP1 protein levels and PAR proteins were detected in mtp53 R273H than in wild-type p53-expressing PDX samples. These results indicate that mtp53 R273H and PARP1 interact with replicating DNA and should be considered as dual biomarkers for identifying breast cancers that may respond to combination PARPi treatments. SIGNIFICANCE: p53 gain-of-function mutant 273H and PARP1 interact with replication forks and could serve as potential biomarkers for breast cancer sensitivity to PARP inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/3/394/F1.large.jpg.
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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.