ArticleProceedings of the National Academy of Sciences of the United States of America2005
Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers, 1 of them a synthesis that pooled it.
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Who cites it
172 citing papers in PubMed, 1 synthesis or guideline pooled it, 278 citations in OpenAlex.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- RPA hyperphosphorylation hinders the resolution of R-loops and G-quadruplex-associated R-loops during RAS-driven senescence.Nucleic acids research · 2026Article
- Break-induced replication is enhanced by a phospho-activated RPA-binding module in Pol32.Nature communications · 2026Article
- Clinicopathological and functional evaluation of replication protein A in epithelial ovarian cancers: A target validation study.Translational oncology · 2026Article
- The RPA-binding domain and the KKRK motif in Rad26ATRIP cooperate at the perturbed DNA replication fork for initiating checkpoint signalling.PLoS genetics · 2026Article
- Conformational modulation of intrinsically disordered transactivation domains for cancer therapy.PNAS nexus · 2025Review
- The functional significance of the RPA- and PCNA-dependent recruitment of Pif1 to DNA.EMBO reports · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- Harmonin homology domain-mediated interaction of RTEL1 helicase with RPA and DNA provides insights into its recruitment to DNA repair sites.Nucleic acids research · 2024Article
- Review
- Phage libraries screening on P53: Yield improvement by zinc and a new parasites-integrating analysis.PloS one · 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
- Structural characterization of human RPA70N association with DNA damage response proteins.eLife · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.PLoS genetics · 2023Article
- Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast.bioRxiv : the preprint server for biology · 2023Article
- Interdomain dynamics in human Replication Protein A regulates kinetics and thermodynamics of its binding to ssDNA.PloS one · 2023Article
- Dynamic structures of intrinsically disordered proteins related to the general transcription factor TFIIH, nucleosomes, and histone chaperones.Biophysical reviews · 2022Review
- The MDMX Acidic Domain Uses Allovalency to Bind Both p53 and MDMX.Journal of molecular biology · 2022Article
- Replication Protein A Utilizes Differential Engagement of Its DNA-Binding Domains to Bind Biologically Relevant ssDNAs in Diverse Binding Modes.Biochemistry · 2022Article
112 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
One of many protein-protein interactions modulated upon DNA damage is that of the single-stranded DNA-binding protein, replication protein A (RPA), with the p53 tumor suppressor. Here we report the crystal structure of RPA residues 1-120 (RPA70N) bound to the N-terminal transactivation domain of p53 (residues 37-57; p53N) and, by using NMR spectroscopy, characterize two mechanisms by which the RPA/p53 interaction can be modulated. RPA70N forms an oligonucleotide/oligosaccharide-binding fold, similar to that previously observed for the ssDNA-binding domains of RPA. In contrast, the N-terminal p53 transactivation domain is largely disordered in solution, but residues 37-57 fold into two amphipathic helices, H1 and H2, upon binding with RPA70N. The H2 helix of p53 structurally mimics the binding of ssDNA to the oligonucleotide/oligosaccharide-binding fold. NMR experiments confirmed that both ssDNA and an acidic peptide mimicking a phosphorylated form of RPA32N can independently compete the acidic p53N out of the binding site. Taken together, our data suggest a mechanism for DNA damage signaling that can explain a threshold response to DNA damage.
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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.