Activation of p53 Facilitates the Target Search in DNA by Enhancing the Target Recognition Probability

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28 Citations (Scopus)

Abstract

Tumor suppressor p53 binds to the target in a genome and regulates the expression of downstream genes. p53 searches for the target by combining three-dimensional diffusion and one-dimensional sliding along the DNA. To examine the regulation mechanism of the target binding, we constructed the pseudo-wild type (pseudo-WT), activated (S392E), and inactive (R248Q) mutants of p53 and observed their target binding in long DNA using single-molecule fluorescence imaging. The pseudo-WT sliding along the DNA showed many pass events over the target and possessed target recognition probability (TRP) of 7 ± 2%. The TRP increased to 18 ± 2% for the activated mutant but decreased to 0% for the inactive mutant. Furthermore, the fraction of the target binding by the one-dimensional sliding among the total binding events increased from 63 ± 9% for the pseudo-WT to 87 ± 2% for the activated mutant. Control of TRP upon activation, as demonstrated here for p53, might be a general activation mechanism of transcription factors.

Original languageEnglish
Pages (from-to)2916-2930
Number of pages15
JournalJournal of Molecular Biology
Volume428
Issue number14
DOIs
Publication statusPublished - 2016 Jul 17

Keywords

  • mutation
  • p53
  • single molecule
  • target binding
  • transcription factor

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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