Abstract

Although the genetic messages in DNA are stored in a linear sequence of base pairs, the genomes of living species do not function in a linear fashion. Gene expression is regulated by DNA elements that often lie far apart along the genomic sequence but come close together during genetic processing. The intervening residues form loops, which are organized by the binding of various proteins. For example, in E. coli the Lac repressor protein assembly binds two DNA operators, separated by 92 or 401 base pairs, and suppresses the formation of gene products involved in the metabolism of lactose. The system also includes several highly abundant architectural proteins, such as Fis and HU, which, upon binding, bend a double-helical turn of DNA by 45 degrees or more. In order to gain a better understanding of the mechanics of DNA looping, we have investigated the effects of various proteins on the configurational properties of fragments of DNA , treating the DNA with elastic potentials t hat consider the intrinsic structure and deformability of successive base pairs and incorporating the known three-dimensional structural effects of various proteins on DNA double-helical structure. The presentation will highlight some of the new models and computational techniques that we have developed to generate the three-dimensional configurations of protein-mediated DNA loops and illustrate new insights gained from this work about the effects of various proteins on DNA topology and the apparent contributions of non-specific binding proteins to gene expression.