Sequence-specific DNA-binding proteins can maintain and regulate cellular functions by accurately and quickly binding to target sequences among large amounts of nontarget DNA. The facilitated diffusion mechanism of DNA-binding proteins—a combination of three-dimensional (3D) diffusion and one-dimensional (1D) sliding along DNA—has been proposed to explain the target binding accuracy and rapidity and has been partially confirmed experimentally. Nonetheless, quantitative elucidation of the mechanism has remained difficult. Furthermore, many additional steps in facilitated diffusion have been proposed. In this review, we introduce the theoretical and experimental studies and the current understanding of facilitated diffusion of DNA-binding proteins. We focused on tumor suppressor p53 as a key protein subject to facilitated diffusion; p53 regulates various cellular processes such as cell cycle arrest, DNA repair, and apoptosis upon binding to a target sequence of DNA after activation by external stress to the cell. We describe the research on the 3D diffusion and 1D sliding of p53 mainly via single-molecule fluorescence microscopy. In addition to the demonstration of the 1D sliding of p53, recent experiments revealed multiple modes of 1D sliding, regulation of the target recognition, and the constant search distance despite changes in the concentrations of divalent cations. Furthermore, rotation-coupled 1D sliding along DNA is suggested. A comparison of parameters of the facilitated diffusion of p53 and those of other DNA-binding proteins characterized so far suggests that the ratio of 3D diffusion and 1D sliding is close to the theoretical optimum of 1:1 for several proteins including p53.

序列特异性DNA结合蛋白可以通过准确，快速地与大量非靶标DNA中的靶标序列结合来维持和调节细胞功能。已经提出了促进DNA结合蛋白扩散的机制-沿着DNA滑动的三维（3D）扩散和一维（1D）结合的作用，以解释靶标结合的准确性和快速性，并已在实验上得到部分证实。然而，对该机制的定量阐明仍然很困难。此外，已经提出了许多促进扩散的附加步骤。在这篇综述中，我们介绍了理论和实验研究以及对DNA结合蛋白促进扩散的当前理解。我们集中研究了抑癌基因p53作为一种易于扩散的关键蛋白。在受到外部压力激活后，p53与DNA的靶序列结合后，会调节各种细胞过程，例如细胞周期停滞，DNA修复和细胞凋亡。我们主要通过单分子荧光显微镜描述了p53在3D扩散和1D滑动方面的研究。除了演示p53的1D滑动外，最近的实验还揭示了1D滑动的多种模式，目标识别的调节以及恒定的搜索距离，尽管二价阳离子的浓度发生了变化。此外，建议沿DNA旋转耦合的1D滑动。比较p53促进扩散的参数和到目前为止已表征的其他DNA结合蛋白的参数，表明3D扩散和1D滑动的比率接近理论最佳值1：