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Tumor Suppressor p53 Slides on DNA with Low Friction and High Stability

Anahita Tafvizi ^*  , Fang Huang , Jason S. Leith  ^* ¶, Alan R. Fersht , Leonid A. Mirny ^* and Antoine M. van Oijen 

^* Harvard-Massachusetts Institute of Technology, Division of Health Sciences and Technology, Cambridge, Massachusetts; Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, Massachusetts; Harvard University, Department of Physics, Cambridge, Massachusetts; ^¶ Harvard University, Program in Biophysics, Boston, Massachusetts; and University of Cambridge, Department of Chemistry, Cambridge, United Kingdom

Correspondence: Address reprint requests and inquiries to Antoine van Oijen, Tel.: 617-432-5586; E-mail: antoine_van_oijen{at}hms.harvard.edu.

The p53 protein, a transcription factor of key importance in tumorigenesis, is suggested to diffuse one-dimensionally along DNA via its C-terminal domain, a process that is proposed to regulate gene activation both positively and negatively. 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.