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Updated: Oct 25, 2025
14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
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Symphony of the DNA flexibility and sequence environment orchestrates p53 binding to its responsive elements
Akkinepally Vanaja1, Sarada Prasanna Mallick2, Umasankar Kulandaivelu3
1Department of Biotechnology, Koneru Lakshmaiah Education Foundation, Guntur 522502, Andhra Pradesh, India; KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Guntur 522502, Andhra Pradesh, India.
Gene
|August 10, 2021
Summary
The p53 tumor suppressor protein
Area of Science:
- Molecular Biology
- Genomics
- Biophysics
Background:
- p53 protein maintains genome integrity by interacting with DNA response elements (REs).
- DNA-protein interactions depend on both base sequence and DNA structural features.
- Understanding these interactions is crucial for comprehending gene regulation and disease.
Purpose of the Study:
- To investigate the fundamental principles governing p53 binding affinity to DNA.
- To analyze how DNA structural alterations (bending, twisting, stretching) influence p53-RE interactions.
- To compare DNA structural requirements for p53 binding with other transcription factors.
Main Methods:
- Utilized high-throughput in vitro relative affinity (HT-Selex) data for p53-REs.
- Analyzed genome-wide p53 binding events using ChIP-Seq experiments.
- Correlated DNA structural parameters with p53 binding affinity.
Main Results:
- Confirmed the significant role of torsional flexibility in p53 binding.
- Identified DNA axial bending, stretching stiffness, propeller twist, and wedge angles as key factors influencing p53 affinity.
- Observed distinct DNA structural environments in p53 target genes and differences between normal and cancer cells.
Conclusions:
- DNA structural features of REs are critical for both in vitro and in vivo p53 binding.
- p53 exhibits unique DNA structural preferences compared to other protein families.
- Differences in DNA flexibility around REs in cancer cells suggest a role in disease pathogenesis.
Keywords:
DNA flexibilityPropeller twistResponse elementStructural featuresWedgeWedge and pioneering capabilities of TP53p53More Related Videos
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