ArticleProceedings of the National Academy of Sciences of the United States of America2012
Sequence-dependent sliding kinetics of p53.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. 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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Who cites it
50 citing papers in PubMed, 91 citations in OpenAlex.
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- Nonspecific vs. specific DNA binding free energetics of a transcription factor domain protein.Biophysical journal · 2023Article
- Single-molecule characterization of target search dynamics of DNA-binding proteins in DNA-condensed droplets.Nucleic acids research · 2023Article
- Single-Molecule Microscopy Meets Molecular Dynamics Simulations for Characterizing the Molecular Action of Proteins on DNA and in Liquid Condensates.Frontiers in molecular biosciences · 2021Review
- Transient binding and jumping dynamics of p53 along DNA revealed by sub-millisecond resolved single-molecule fluorescence tracking.Scientific reports · 2020Article
- How p53 Molecules Solve the Target DNA Search Problem: A Review.International journal of molecular sciences · 2020Review
- Liquid-like droplet formation by tumor suppressor p53 induced by multivalent electrostatic interactions between two disordered domains.Scientific reports · 2020Article
- CRISPR/Cas9 searches for a protospacer adjacent motif by lateral diffusion.The EMBO journal · 2019Article
- Considering Abundance, Affinity, and Binding Site Availability in the NF-κB Target Selection Puzzle.Frontiers in immunology · 2019Review
- Mechanisms of Protein Search for Targets on DNA: Theoretical Insights.Molecules (Basel, Switzerland) · 2018Article
- Intrinsically disordered domain of tumor suppressor p53 facilitates target search by ultrafast transfer between different DNA strands.Nucleic acids research · 2018Article
- Sliding of a single lac repressor protein along DNA is tuned by DNA sequence and molecular switching.Nucleic acids research · 2018Article
- Two-step interrogation then recognition of DNA binding site by Integration Host Factor: an architectural DNA-bending protein.Nucleic acids research · 2018Article
- Single-molecule DNA unzipping reveals asymmetric modulation of a transcription factor by its binding site sequence and context.Nucleic acids research · 2018Article
- Energetic funnel facilitates facilitated diffusion.Nucleic acids research · 2018Article
- Cohesin SA2 is a sequence-independent DNA-binding protein that recognizes DNA replication and repair intermediates.The Journal of biological chemistry · 2018Article
- A new era of studying p53-mediated transcription activation.Transcription · 2018Article
- Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proper timing of gene expression requires that transcription factors (TFs) efficiently locate and bind their target sites within a genome. Theoretical studies have long proposed that one-dimensional sliding along DNA while simultaneously reading its sequence can accelerate TF's location of target sites. Sliding by prokaryotic and eukaryotic TFs were subsequently observed. More recent theoretical investigations have argued that simultaneous reading and sliding is not possible for TFs without their possessing at least two DNA-binding modes. The tumor suppressor p53 has been shown to slide on DNA, and recent experiments have offered structural and single molecule support for a two-mode model for the protein. If the model is applicable to p53, then the requirement that TFs be able to read while sliding implies that noncognate sites will affect p53's mobility on DNA, which will thus be generally sequence-dependent. Here, we confirm this prediction with single-molecule microscopy measurements of p53's local diffusivity on noncognate DNA. We show how a two-mode model accurately predicts the variation in local diffusivity, while a single-mode model does not. We further determine that the best model of sequence-specific binding energy includes terms for "hemi-specific" binding, with one dimer of tetrameric p53 binding specifically to a half-site and the other binding nonspecifically to noncognate DNA. Our work provides evidence that the recognition by p53 of its targets and the timing thereof can depend on its noncognate binding properties and its ability to change between multiple modes of binding, in addition to the much better-studied effects of cognate-site binding.
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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.