White The investigator studies the structure of closed circular DNA. The theoretical approach employs displacement based Finite Element Analysis (FEA), a well-established technique for obtaining solutions to engineering problems in nonlinear solid mechanics. FEA is used to describe closed DNAs containing multiple coplanar bends that are in-phase; containing bends that do not lie in the same plane; and containing bends are distributed both symmetrically and asymmetrically. It is predicted that the twist distribution is uniform throughout the regions between the bends; that the fraction of the linking number change (DLk) converted into writhe increases with the number of bends; and that the regional contribution to the writhe increases if the bends are clustered in that region. Methods are devised for solving the problem of avoidance of passage of the DNA strand through itself as DLk becomes greater than 12. This includes a novel approach, the use of special contact elements (gap elements). These have the property that when the gap distance reduces to some specified value, nodal motion constraints are relaxed if the nodes subsequently tend to separate. Finally, methods are developed for decomposing changes in DLk into changes in writhe and twist. Biologically, closed circular DNA is one of the most important structural forms of DNA. This includes not only free DNA molecules, such as the plasmids used in all genetic engineering experiments, but chromatin as well, which is now known to be divided into domains of supercoiling. Bent regions in DNA appear to be significant in regulating the initiating of transcription. This project provides the physical basis for understanding the combined effects of these two structures. DNA is not only a repository for genetic information but also is involved in many aspects of the expression of this information. For example, it is often necessary to bring together portions of the DNA molecule that lie at considerable distances from each other along the DNA contour. This juxtaposition of distant genetic elements makes possible the expression of biological information that is not otherwise possible. This process is accomplished by forming a loop, in which the two elements that are to be brought together interact at the site of loop closure. The bringing together of these distant genes depends in a sensitive way upon the length of the DNA piece that separates them and upon the helical periodicity. This project shows how the presence of internal bends in DNA within the loop fundamentally changes how distant segments are brought together. The distribution of these internal bends can thus have profound biological consequences.
