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Updated: Sep 30, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Specific interaction of p53 with target binding sites is determined by DNA conformation and is regulated by the
Thomas Göhler1, Maurice Reimann, Dimitry Cherny
1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie, Universität Hamburg, Martinistrasse 52, Hamburg D-20251, Germany.
Abstract:
Transcriptional activation of p53-regulated genes is initiated by sequence-specific DNA binding of p53 to target binding sites. Regulation of sequence-specific DNA binding is complex and occurs at various levels. We demonstrate that DNA topology is an important parameter for regulating the selective and highly specific interaction of p53 with its target binding sites. Specific binding of wild-type p53 is greatly enhanced when cognate binding sites are present in a non-linear stem-loop conformation. The C-terminal domain plays a key role in regulating the specific interactions of p53 with target binding sites in a DNA conformation-dependent manner. The C-terminal domain is required for binding to target sites in a non-linear DNA conformation in contrast to the strong inhibitory effects of the C terminus on p53 interaction with linear DNA. We propose that selective binding of p53 to various promoters may be determined by the DNA conformation within p53 cognate sites.
Insights
DNA topology influences tumor suppressor p53
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- p53's transcriptional activation relies on sequence-specific DNA binding.
- Regulation of p53 DNA binding is multifaceted and occurs at multiple levels.
Purpose of the Study:
- To investigate the role of DNA topology in regulating p53's selective DNA binding.
- To elucidate how DNA conformation affects p53-target site interactions.
Main Methods:
- Analysis of p53 binding to DNA with varying topological properties.
- Characterization of the C-terminal domain's role in DNA conformation-dependent binding.
Main Results:
- Specific binding of wild-type p53 is significantly enhanced by non-linear stem-loop DNA conformations.
- The C-terminal domain is crucial for p53 binding to non-linear DNA but inhibits binding to linear DNA.
Conclusions:
- DNA topology is a critical regulator of p53's selective and specific binding to target sites.
- The conformation of p53 cognate sites may determine selective p53 binding to various promoters.
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