Disruption of Protein-Mediated DNA Looping by Tension in the Substrate DNA

¹ University of Michigan

^* To whom correspondence should be addressed. E-mail: meiners{at}umich.edu.

Submitted on October 15, 2004
Revised on December 17, 2004
Accepted on 28 December 2004

	Abstract

Protein-mediated DNA looping is important in a variety of biological processes including gene regulation and genetic transformation. While the biochemistry of loop formation is well established, the mechanics of loop closure in a constrained cellular environment has received less attention. Recent single molecule measurements show that mechanical constraints have a significant impact on DNA looping and motivate the need for a more comprehensive characterization of the effects of tension. By modeling DNA as a wormlike chain, we calculate how continuous stretching of the substrate DNA affects the loop formation probability. We find that when the loop size is greater than 100bp a tension of 500 femtonewtons can increase the time required for loop closure by two orders of magnitude. This force is small compared to the piconewton forces that are associated with RNA polymerases and other molecular motors, indicating that intracellular mechanical forces might affect transcriptional regulation. In contrast to existing theory, we find that for loops smaller than 200bp the effect of tension is partly dependent on the relative orientation of the DNA-binding domains in the linker protein. Our results provide perspective on recent DNA looping experiments and suggestions for future micromechanical studies.

Key Words: DNA Looping, DNA Mechanics, DNA-Protein Interactions, Gene Regulation, Micromechanical Experiments, Tension

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