Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 2, Pages 563-568Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1016020107
Keywords
recognition; response element; transcription factor
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Funding
- National Science Foundation
- National Institutes of Health
- National Cancer Institute through Physical Sciences in Oncology Center at MIT
- MRC [MC_UP_A024_1010, MC_EX_G0901534] Funding Source: UKRI
- Medical Research Council [MC_UP_A024_1010, MC_EX_G0901534] Funding Source: researchfish
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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.
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