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The p53 C terminus controls site-specific DNA binding and promotes structural changes within the central DNA binding

Oleg Laptenko1, Idit Shiff2, Will Freed-Pastor1

  • 1Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Molecular Cell
|March 22, 2015
PubMed

Insights

The p53 C-terminal domain (CTD) is crucial for DNA binding, enabling sequence-dependent interactions and stable complex formation, especially at non-canonical sites.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Transcription factors, like p53, bind DNA to regulate gene expression.
  • The p53 core DNA binding domain (DBD) is known for site-specific binding.
  • The role of the p53 C-terminal domain (CTD) in DNA binding remains unclear.

Purpose of the Study:

  • To investigate the DNA-binding properties of p53 C-terminal domain (CTD) variants.
  • To elucidate the contribution of the CTD to p53-DNA interactions.
  • To understand how CTD modifications or deletions affect DNA binding.

Main Methods:

  • In vitro biochemical analyses of p53 CTD variants.
  • In vivo DNA binding experiments.
  • Analysis of p53 binding to canonical and divergent DNA sequences.

Main Results:

  • The p53 CTD mediates sequence-dependent DNA binding, sensitive to modifications or deletions.
  • CTD dependence increases as p53 binding sites deviate from consensus sequences.
  • The CTD facilitates stable p53-DNA complex formation at divergent sites through DBD conformational changes.

Conclusions:

  • The p53 CTD plays a significant, sequence-dependent role in DNA binding.
  • CTD function is critical for p53 to bind non-canonical DNA sites.
  • DNA-induced conformational changes in the DBD, mediated by the CTD, are key for stable binding.

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