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

Yuji Itoh, Agato Murata, Seiji Sakamoto, Kei Nanatani, Takehiko Wada, Satoshi Takahashi, Kiyoto Kamagata

Research output: Contribution to journalArticlepeer-review

20 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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