Facilitation of DNA loop formation by protein-DNA non-specific interactions

Abstract

Complex DNA topological structures, including polymer loops, are frequently observed in biological processes when protein molecules simultaneously bind to several distant sites on DNA. However, the molecular mechanisms of formation of these systems remain not well understood. Existing theoretical studies focus only on specific interactions between protein and DNA molecules at target sequences. However, the electrostatic origin of primary protein-DNA interactions suggests that interactions of proteins with all DNA segments should be considered. Here we theoretically investigate the role of non-specific interactions between protein and DNA molecules on the dynamics of loop formation. Our approach is based on analyzing a discrete-state stochastic model via a method of first-passage probabilities supplemented by Monte Carlo computer simulations. It is found that depending on a protein sliding length during the non-specific binding event three different dynamic regimes of the DNA loop formation might be observed. In addition, the loop formation time might be optimized by varying the protein sliding length, the size of the DNA molecule, and the position of the specific target sequences on DNA. Our results demonstrate the importance of non-specific protein-DNA interactions in the dynamics of DNA loop formations. Several quantitative predictions that can be experimentally tested are also presented.

arXiv comment8 pages, 6 figures

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Cited by in corpus (2)

• The Effect of Obstacles in Multi-Site Protein Target Search with DNA Looping
• Bending short DNAs as transversely isotropic rings in series