Project Desription
As provided by the DIMACS REU Program

Project#: DDD2009-09

Mentor: Wilma Olson, Chemistry

Project Title: Protein-Induced DNA Looping

Many genetic processes are mediated by proteins that bind at separate, often widely spaced, sites on the double helix, tethering the intervening DNA into a loop. Examples of these processes include gene expression and its control, DNA replication, genetic rearrangements, multi-site cutting by restriction enzymes, and DNA packaging. A DNA loop stabilized by such long-range protein-protein contacts constitutes a discrete topological unit. As long as the ends of the DNA stay in place and the duplex remains unbroken, the linking number, Lk, or number of times the two strands of the double helix wrap around one another, is conserved. This constraint in Lk underlies the well known supercoiling of DNA: the stress induced by positioning the ends of the polymer in locations other than the natural (relaxed) state perturbs the overall coiling of the chain axis and/or the twisting of successive base-pairs in the invervening parts of the chain. As a first step in understanding the effects of specific proteins and drugs on DNA looping, we propose to study the imposed bending and twisting of neighboring base pairs in known complexes of proteins and drugs with double helical DNA stored in the Nucleic Acid Database. By subjecting a DNA segment of the same chain length as that found in a given complex to the observed orientation, displacement, and superhelical stress and setting the elastic moduli to sufficiently high values, we can use existing programs to stimulate the presence of a rigidly bound molecule at arbitrary positions on circular DNA molecules or to model specific systems in which DNA looping plays an important role, e.g., the lac repressor-operator assembly in EscherichiaAOcoli. One student could devote a summer project to the collection of geometric information. Other students could apply this information to simulations of DNA loops and folds in subsequent years.