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Two- and Three-Dimensional Live Cell Imaging of DNA Damage Response Proteins
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Published on: September 28, 2012

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Activation of p53 sequence-specific DNA binding by short single strands of DNA requires the p53 C-terminus

J Jayaraman1, C Prives

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

Cell
|June 30, 1995
PubMed

Insights

Short single DNA strands enhance tumor suppressor p53 protein

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The p53 tumor suppressor protein is crucial in cellular DNA damage response.
  • p53 acts as a sequence-specific transcriptional activator, regulating cell cycle and apoptosis.
  • Understanding p53's DNA binding mechanisms is vital for cancer research.

Purpose of the Study:

  • To investigate the role of single-stranded DNA in modulating p53's sequence-specific DNA binding.
  • To elucidate the contribution of the p53 C-terminus in this DNA binding regulation.

Main Methods:

  • Demonstrated p53 binding to response elements in supercoiled DNA.
  • Utilized truncated p53 lacking the C-terminal domain to assess its role.
  • Employed a C-terminal peptide to study its effect on p53 DNA binding in trans.

Main Results:

  • Short single DNA strands significantly stimulate p53 binding to response elements.
  • Single-stranded DNA did not enhance binding in p53 lacking the C-terminal domain.
  • A peptide of the p53 C-terminus dramatically stimulated sequence-specific DNA binding.

Conclusions:

  • The p53 C-terminus plays a key role in recognizing DNA damage-induced structures.
  • This interaction positively regulates p53's sequence-specific DNA binding.
  • Suggests a novel mechanism for p53 activation in response to DNA damage.

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