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

研究成果: Article査読

25 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2916-2930
ページ数15
ジャーナルJournal of Molecular Biology
428
14
DOI
出版ステータスPublished - 2016 7 17

ASJC Scopus subject areas

  • 構造生物学
  • 分子生物学

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