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Yeast As a Chassis for Developing Functional Assays to Study Human P53
14:57

Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

DNA modification with cisplatin affects sequence-specific DNA binding of p53 and p73 proteins in a target

Hana Pivonková1, Petr Pecinka, Pavla Cesková

  • 1Institute of Biophysics, Academy of Sciences of the Czech Republic, Brno, Czech Republic.

The FEBS Journal
|September 20, 2006
PubMed

Insights

The antitumor drug cisplatin affects p53 and p73 protein binding to DNA differently based on DNA sequence. Cisplatin’s impact on protein-DNA interactions is linked to specific DNA motifs, influencing cellular pathways.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • The p53 and p73 proteins are crucial transcription factors involved in cell cycle control, development, and apoptosis.
  • These proteins bind to specific DNA sequences known as response elements.
  • Previous studies indicated that cisplatin inhibits p53 binding to DNA.

Purpose of the Study:

  • To investigate how global DNA modification by cisplatin affects the binding of p53 and p73 proteins to various DNA response elements.
  • To determine the role of specific DNA sequences and cisplatin adducts in modulating protein-DNA interactions.

Main Methods:

  • Comparative analysis of p53 and p73 protein binding to different p53 DNA-binding sites after cisplatin treatment.
  • Correlation of binding inhibition with the presence of specific sequence motifs (GG and AG doublets) sensitive to cisplatin adduct formation.

Main Results:

  • Cisplatin's inhibitory effect on p53 and p73 binding varied significantly depending on the nucleotide sequence of the DNA target site.
  • The sensitivity of protein-DNA binding to cisplatin correlated with the presence of GG and AG motifs within the binding sites.
  • Mutated DNA sites lacking these motifs showed negligible inhibition of protein binding after cisplatin treatment.

Conclusions:

  • Cisplatin-induced DNA adducts within specific sequence motifs are the primary cause of inhibition for p53 and p73 sequence-specific DNA binding.
  • Differential effects of cisplatin on protein-DNA recognition may influence regulatory pathways in cells treated with this anticancer drug.

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