A single-molecule characterization of p53 search on DNA
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Mirny_A single-molecule.pdf
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Author(s)
Tafvizi, Anahita
Huang, Fang
Fersht, Alan R.
Mirny, Leonid A.
van Oijen, Antoine M.
Date Issued
January 2011
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Tafvizi, Anahita, Fang Huang, Alan R. Fersht, Leonid A. Mirny, and Antoine M. van Oijen. "A single-molecule characterization of p53 search on DNA." Proceedings of the National Academy of Sciences of the United States of America (PNAS), 108:2 (2011), p.563–568.
Version
Final published version
Abstract
The tumor suppressor p53 slides along DNA while searching for its cognate site. Central to this process is the basic C-terminal domain, whose regulatory role and its coordination with the core DNA-binding domain is highly debated. Here we use single-molecule techniques to characterize the search process and disentangle the roles played by these two DNA-binding domains in the search process. We demonstrate that the C-terminal domain is capable of rapid translocation, while the core domain is unable to slide and instead hops along DNA. These findings are integrated into a model, in which the C-terminal domain mediates fast sliding of p53, while the core domain samples DNA by frequent dissociation and reassociation, allowing for rapid scanning of long DNA regions. The model further proposes how modifications of the C-terminal domain can activate “latent” p53 and reconciles seemingly contradictory data on the action of different domains and their coordination.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Physics
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1016020107
