ArticleProceedings of the National Academy of Sciences of the United States of America1999
p53-induced DNA bending and twisting: p53 tetramer binds on the outer side of a DNA loop and increases DNA twisting.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
50 citing papers in PubMed, 128 citations in OpenAlex.
- Dominant-Negative Effects of p53 R337 Variants in Li-Fraumeni Syndrome: Impact on Tetramer Formation and Transcriptional Activity.Chembiochem : a European journal of chemical biology · 2025Article
- TowardsbioRxiv : the preprint server for biology · 2025Article
- NMR investigation of FOXO4-DNA interaction for discriminating target and non-target DNA sequences.Communications biology · 2024Article
- The TOPOVIBL meiotic DSB formation protein: new insights from its biochemical and structural characterization.Nucleic acids research · 2024Article
- Detection of new pioneer transcription factors as cell-type-specific nucleosome binders.eLife · 2024Article
- Article
- Rely on Each Other: DNA Binding Cooperativity Shapes p53 Functions in Tumor Suppression and Cancer Therapy.Cancers · 2021Review
- Temporal gene regulation by p53 is associated with the rotational setting of its binding sites in nucleosomes.Cell cycle (Georgetown, Tex.) · 2021Article
- Single molecule studies reveal that p53 tetramers dynamically bind response elements containing one or two half sites.Scientific reports · 2020Article
- Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer.FEBS open bio · 2019Article
- Mechanisms of transcriptional regulation by p53.Cell death and differentiation · 2018Review
- Diverse p53/DNA binding modes expand the repertoire of p53 response elements.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Reviving the guardian of the genome: Small molecule activators of p53.Pharmacology & therapeutics · 2017Review
- Structural Evolution and Dynamics of the p53 Proteins.Cold Spring Harbor perspectives in medicine · 2017Review
- Article
- Recognition of Local DNA Structures by p53 Protein.International journal of molecular sciences · 2017Review
- Electrochemistry of nonconjugated proteins and glycoproteins. Toward sensors for biomedicine and glycomics.Chemical reviews · 2015Review
- Time-Resolved Fluorescence Anisotropy Study of the Interaction Between DNA and a Peptide Truncated from the p53 Protein Core Domain.Journal of fluorescence · 2014Article
- The nucleolar protein Myb-binding protein 1A (MYBBP1A) enhances p53 tetramerization and acetylation in response to nucleolar disruption.The Journal of biological chemistry · 2014Article
- Conformations of p53 response elements in solution deduced using site-directed spin labeling and Monte Carlo sampling.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
DNA binding activity of p53 is crucial for its tumor suppressor function. Our recent studies have shown that four molecules of the DNA binding domain of human p53 (p53DBD) bind the response elements with high cooperativity and bend the DNA. By using A-tract phasing experiments, we find significant differences between the bending and twisting of DNA by p53DBD and by full-length human wild-type (wt) p53. Our data show that four subunits of p53DBD bend the DNA by 32-36 degrees, whereas wt p53 bends it by 51-57 degrees. The directionality of bending is consistent with major groove bends at the two pentamer junctions in the consensus DNA response element. More sophisticated phasing analyses also demonstrate that p53DBD and wt p53 overtwist the DNA response element by approximately 35 degrees and approximately 70 degrees, respectively. These results are in accord with molecular modeling studies of the tetrameric complex. Within the constraints imposed by the protein subunits, the DNA can assume a range of conformations resulting from correlated changes in bend and twist angles such that the p53-DNA tetrameric complex is stabilized by DNA overtwisting and bending toward the major groove at the CATG tetramers. This bending is consistent with the inherent sequence-dependent anisotropy of the duplex. Overall, the four p53 moieties are placed laterally in a staggered array on the external side of the DNA loop and have numerous interprotein interactions that increase the stability and cooperativity of binding. The novel architecture of the p53 tetrameric complex has important functional implications including possible p53 interactions with chromatin.
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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.