Tumor suppressor p53 slides on DNA with low friction and high stability

Authors

Anahita Tafvizi, Harvard Medical School
Fang Huang, University of Cambridge
Jason S. Leith, Harvard Medical School
Alan R. Fersht, University of Cambridge
Leonid A. Mirny, Harvard-Massachusetts Institute of Technology
Antoine M. van Oijen, Harvard Medical SchoolFollow

RIS ID

94200

Publication Details

Tafvizi, A., Huang, F., Leith, J. S., Fersht, A. R., Mirny, L. A. & van Oijen, A. M. (2008). Tumor suppressor p53 slides on DNA with low friction and high stability. Biophysical Journal, 95 (1), L01-L03.

Abstract

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.