This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Coppey, M. Articles by Moreau, M. Search for Related Content PubMed PubMed Citation Articles by Coppey, M. Articles by Moreau, M.

Kinetics of Target Site Localization of a Protein on DNA: A Stochastic Approach

M. Coppey ^*, O. Bénichou , R. Voituriez ^* and M. Moreau ^*

^* Laboratoire de Physique Théorique des Liquides, Université Pierre et Marie Curie, Paris, France; and Laboratoire de Physique de la Matière Condensée, Collège de France, Paris, France

Correspondence: Address reprint requests to Mathieu Coppey, Tel.: 33-1-442-77291; E-mail: coppey{at}lptl.jussieu.fr.

It is widely recognized that the cleaving rate of a restriction enzyme on target DNA sequences is several orders-of-magnitude faster than the maximal one calculated from the diffusion-limited theory. It was therefore commonly assumed that the target site interaction of a restriction enzyme with DNA has to occur via two steps: one-dimensional diffusion along a DNA segment, and long-range jumps coming from association-dissociation events. We propose here a stochastic model for this reaction which comprises a series of one-dimensional diffusions of a restriction enzyme on nonspecific DNA sequences interrupted by three-dimensional excursions in the solution until the target sequence is reached. This model provides an optimal finding strategy which explains the fast association rate. Modeling the excursions by uncorrelated random jumps, we recover the expression of the mean time required for target site association to occur given by Berg et al. in 1981, and we explicitly give several physical quantities describing the stochastic pathway of the enzyme. For competitive target sites we calculate two quantities: processivity and preference. By comparing these theoretical expressions to recent experimental data obtained for EcoRV-DNA interaction, we quantify: 1), the mean residence time per binding event of EcoRV on DNA for a representative one-dimensional diffusion coefficient; 2), the average lengths of DNA scanned during the one-dimensional diffusion (during one binding event and during the overall process); and 3), the mean time and the mean number of visits needed to go from one target site to the other. Further, we evaluate the dynamics of DNA cleavage with regard to the probability for the restriction enzyme to perform another one-dimensional diffusion on the same DNA substrate following a three-dimensional excursion.

This article has been cited by other articles:

				I. Bonnet, A. Biebricher, P.-L. Porte, C. Loverdo, O. Benichou, R. Voituriez, C. Escude, W. Wende, A. Pingoud, and P. Desbiolles Sliding and jumping of single EcoRV restriction enzymes on non-cognate DNA Nucleic Acids Res., July 1, 2008; 36(12): 4118 - 4127. [Abstract] [Full Text] [PDF]

				Z. Wunderlich and L. A. Mirny Spatial effects on the speed and reliability of protein-DNA search Nucleic Acids Res., June 1, 2008; 36(11): 3570 - 3578. [Abstract] [Full Text] [PDF]

				S. Condamin, V. Tejedor, R. Voituriez, O. Benichou, and J. Klafter Probing microscopic origins of confined subdiffusion by first-passage observables PNAS, April 15, 2008; 105(15): 5675 - 5680. [Abstract] [Full Text] [PDF]

				C. Lou, X. Yang, X. Liu, B. He, and Q. Ouyang A Quantitative Study of {lambda}-Phage SWITCH and Its Components Biophys. J., April 15, 2007; 92(8): 2685 - 2693. [Abstract] [Full Text] [PDF]

				J. S. van Zon, M. J. Morelli, S. Tanase-Nicola, and P. R. ten Wolde Diffusion of Transcription Factors Can Drastically Enhance the Noise in Gene Expression Biophys. J., December 15, 2006; 91(12): 4350 - 4367. [Abstract] [Full Text] [PDF]

				T. Hu, A. Yu. Grosberg, and B. I. Shklovskii How Proteins Search for Their Specific Sites on DNA: The Role of DNA Conformation Biophys. J., April 15, 2006; 90(8): 2731 - 2744. [Abstract] [Full Text] [PDF]

				I. M. Sokolov, R. Metzler, K. Pant, and M. C. Williams Target Search of N Sliding Proteins on a DNA Biophys. J., August 1, 2005; 89(2): 895 - 902. [Abstract] [Full Text] [PDF]

				H.-X. Zhou A Model for the Mediation of Processivity of DNA-Targeting Proteins by Nonspecific Binding: Dependence on DNA Length and Presence of Obstacles Biophys. J., March 1, 2005; 88(3): 1608 - 1615. [Abstract] [Full Text] [PDF]