Tumor suppressor p53 slides on DNA with low friction and high stability
Anahita Tafvizi 1, Fang Huang 2, Jason S. Leith 1, Alan R. Fersht 2, Leonid A. Mirny 3 and Antoine M. van Oijen 1*
1 Harvard Medical School
2 University of Cambridge
3 Massachusets Institute of Technology
* To whom correspondence should be addressed. E-mail: antoine_van_oijen{at}hms.harvard.edu.
Submitted on March 24, 2008
Revised on March 26, 2008
Accepted on 8 April 2008
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Abstract |
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The p53 protein, a transcription factor of key importance in tumorigenesis, is suggested to diffuse one-dimensionally along DNA (1) via its C-terminal domain, a process that is proposed to regulate both positively and negatively gene activation. There has been no direct observation of p53 moving along DNA, however, and little is known about the mechanism and rate of its translocation. Here, we use single-molecule techniques to visualize, in real time, the one-dimensional diffusion of p53 along DNA. The one-dimensional diffusion coefficient is measured to be close to the theoretical limit, indicative of movement along a free energy landscape with low activation barriers. We further investigate the mechanism of translocation and determine that p53 is capable of sliding-moving along DNA while in continuous contact with the duplex, rather than through a series of hops between nearby bases.
Key Words:
Single-molecule studies, facilitated diffusion, p53, sliding
