A single-molecule characterization of p53 search on DNA
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 pro...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2016
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| Online Access: | http://hdl.handle.net/1721.1/102871 https://orcid.org/0000-0002-0785-5410 |
| _version_ | 1811069532268134400 |
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| author | Tafvizi, Anahita Huang, Fang Fersht, Alan R. Mirny, Leonid A. van Oijen, Antoine M. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Tafvizi, Anahita Huang, Fang Fersht, Alan R. Mirny, Leonid A. van Oijen, Antoine M. |
| author_sort | Tafvizi, Anahita |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T08:11:52Z |
| format | Article |
| id | mit-1721.1/102871 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T08:11:52Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1028712022-09-23T11:34:20Z A single-molecule characterization of p53 search on DNA Tafvizi, Anahita Huang, Fang Fersht, Alan R. Mirny, Leonid A. van Oijen, Antoine M. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Physics Tafvizi, Anahita Mirny, Leonid A. 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. National Science Foundation (U.S.) National Institutes of Health (U.S.) National Cancer Institute (U.S.). Physical Sciences-Oncology Center 2016-06-02T20:55:13Z 2016-06-02T20:55:13Z 2011-01 2010-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/102871 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. https://orcid.org/0000-0002-0785-5410 en_US http://dx.doi.org/10.1073/pnas.1016020107 Proceedings of the National Academy of Sciences 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. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Tafvizi, Anahita Huang, Fang Fersht, Alan R. Mirny, Leonid A. van Oijen, Antoine M. A single-molecule characterization of p53 search on DNA |
| title | A single-molecule characterization of p53 search on DNA |
| title_full | A single-molecule characterization of p53 search on DNA |
| title_fullStr | A single-molecule characterization of p53 search on DNA |
| title_full_unstemmed | A single-molecule characterization of p53 search on DNA |
| title_short | A single-molecule characterization of p53 search on DNA |
| title_sort | single molecule characterization of p53 search on dna |
| url | http://hdl.handle.net/1721.1/102871 https://orcid.org/0000-0002-0785-5410 |
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