Journal
JOURNAL OF MOLECULAR BIOLOGY
Volume 428, Issue 14, Pages 2916-2930Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2016.06.001
Keywords
transcription factor; p53; mutation; single molecule; target binding
Categories
Funding
- JSPS KAENHI [JP26840045, JP24113701, JP15H01625, JP16K07313, JP25104007]
- Basic Science Research Projects from The Sumitomo Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [15H01625, 26282136, 16K07313, 16H02289, 25104007] Funding Source: KAKEN
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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. (C) 2016 Elsevier Ltd. All rights reserved.
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