Abstract
Homologous recombination is repressed by the binding of p53 to Rad51. We identified by fluorescence and NMR spectroscopy that peptides corresponding to residues 179-190 of Rad51 bind to the core domain of p53 in a site that overlaps with its specific DNA binding site. The p53 site is quite promiscuous, since it also binds peptides derived from 53BP1, 53BP2, Hif-1alpha, and BCL-X(L) in overlapping regions. Binding is mediated mainly by a strong, nonspecific, electrostatic component and is fine tuned by specific interactions. Competition of the different proteins with each other and with specific DNA for a single site in p53 could be a factor in regulation of its activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anisotropy
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Apoptosis Regulatory Proteins
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Binding Sites
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Binding, Competitive
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Carrier Proteins / chemistry
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DNA / chemistry
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DNA-Binding Proteins / chemistry*
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DNA-Binding Proteins / metabolism
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Dose-Response Relationship, Drug
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Humans
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Intracellular Signaling Peptides and Proteins / chemistry
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Ions
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Kinetics
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Mutation
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Peptides / chemistry
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Phosphoproteins / chemistry
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Rad51 Recombinase
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Recombination, Genetic
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Spectrometry, Fluorescence
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Static Electricity
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Tumor Suppressor Protein p53 / chemistry*
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Tumor Suppressor Protein p53 / metabolism
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Tumor Suppressor p53-Binding Protein 1
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Ultracentrifugation
Substances
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Apoptosis Regulatory Proteins
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Carrier Proteins
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DNA-Binding Proteins
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Intracellular Signaling Peptides and Proteins
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Ions
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Peptides
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Phosphoproteins
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TP53BP1 protein, human
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TP53BP2 protein, human
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Tumor Suppressor Protein p53
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Tumor Suppressor p53-Binding Protein 1
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DNA
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RAD51 protein, human
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Rad51 Recombinase