The Rich World of p53 DNA Binding Targets: The Role of DNA Structure
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Updated: Jan 4, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Václav Brázda1, Miroslav Fojta1
1Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czech Republic.
Abstract:
The tumor suppressor functions of p53 and its roles in regulating the cell cycle, apoptosis, senescence, and metabolism are accomplished mainly by its interactions with DNA. p53 works as a transcription factor for a significant number of genes. Most p53 target genes contain so-called p53 response elements in their promoters, consisting of 20 bp long canonical consensus sequences. Compared to other transcription factors, which usually bind to one concrete and clearly defined DNA target, the p53 consensus sequence is not strict, but contains two repeats of a 5'RRRCWWGYYY3' sequence; therefore it varies remarkably among target genes. Moreover, p53 binds also to DNA fragments that at least partially and often completely lack this consensus sequence. p53 also binds with high affinity to a variety of non-B DNA structures including Holliday junctions, cruciform structures, quadruplex DNA, triplex DNA, DNA loops, bulged DNA, and hemicatenane DNA. In this review, we summarize information of the interactions of p53 with various DNA targets and discuss the functional consequences of the rich world of p53 DNA binding targets for its complex regulatory functions.
Insights
The tumor suppressor protein p53 (also known as TP53) interacts with DNA, regulating cell functions. This review details p53
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The p53 protein is a crucial tumor suppressor involved in cell cycle regulation, apoptosis, senescence, and metabolism.
- p53 functions primarily as a transcription factor, binding to specific DNA sequences to regulate gene expression.
Purpose of the Study:
- To review the diverse DNA binding targets of p53.
- To discuss the functional implications of p53's extensive DNA interactions for its regulatory roles.
Main Methods:
- Literature review of studies on p53-DNA interactions.
- Analysis of p53 binding to canonical and non-canonical DNA sequences.
- Examination of p53 binding to non-B DNA structures.
Main Results:
- p53 binds to a variety of DNA targets, not limited to strict consensus sequences.
- The p53 consensus binding site exhibits variability across different target genes.
- p53 demonstrates high-affinity binding to numerous non-B DNA structures, including Holliday junctions and quadruplex DNA.
Conclusions:
- p53's interaction with a wide range of DNA structures contributes to its complex tumor suppressor functions.
- Understanding the diversity of p53 DNA binding is essential for comprehending its multifaceted regulatory roles in cellular processes.
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