DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

E Kim1, N Albrechtsen, W Deppert

  • 1Heinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Germany.

Oncogene
|August 14, 1997
PubMed

Insights

The tumor suppressor p53 binds DNA in various forms, including double-helix and non-B-DNA structures. DNA conformation, influenced by sequence, is key for p53 binding, potentially modulated by p53

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The tumor suppressor p53 protein regulates gene transcription through sequence-specific DNA binding.
  • p53 DNA binding is a critical process tightly controlled by post-translational modifications, particularly in its carboxy-terminal regulatory domain.
  • The structural conformation of DNA may influence the binding affinity and specificity of transcription factors like p53.

Purpose of the Study:

  • To investigate the impact of DNA structure on the sequence-specific DNA binding of the tumor suppressor p53.
  • To determine if p53 can bind to p53 consensus elements in different conformational states, including double-helical and non-B-DNA structures.

Main Methods:

  • Analysis of p53 binding to p53 consensus elements with varying DNA conformations.
  • Examination of sequence symmetry and sequence environment to understand their influence on DNA structure adoption.

Main Results:

  • p53 demonstrates the capacity to bind consensus elements in both double-helical and alternative non-B-DNA structures.
  • The propensity of a DNA consensus element to adopt specific conformations is dictated by its sequence symmetry and surrounding sequence context.
  • Sequence-specific DNA binding by p53 is significantly influenced by the conformational state of its target DNA.

Conclusions:

  • The conformational status of target DNA is a crucial determinant for sequence-specific DNA binding by p53.
  • Modifications in the carboxy-terminal regulatory region of p53 likely dictate its preference for particular DNA conformations.
  • This suggests a model where DNA structure plays a vital role in regulating p53's transcriptional activity.

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