Tumor suppressor p53 slides on DNA with low friction and high stability
Tumor suppressor p53 slides on DNA with low friction and high stability
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DOI：
10.1529/biophysj.108.134122
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发表时间：
2008-07-01
影响因子：
3.4
通讯作者：
van Oijen, Antoine M.
中科院分区：
文献类型：
--
作者：
Tafvizi, Anahita;Huang, Fang;van Oijen, Antoine M.
p53蛋白是一种在肿瘤发生中起关键作用的转录因子，它可以通过其C-末端结构域沿DNA沿着一维扩散，这一过程被认为可以正向和负向调节基因激活。然而，还没有直接观察到p53沿着沿着DNA移动，并且对其易位的机制和速率知之甚少。在这里，我们使用单分子技术可视化，在真实的时间，一维扩散的p53沿着DNA。一维扩散系数被测量为接近理论极限，指示沿着具有低活化势垒的自由能景观的运动。我们进一步研究了易位的机制，并确定p53能够在与双链体连续接触时沿着DNA滑动移动沿着，而不是通过附近碱基之间的一系列跳跃。
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.