Recent results from Dr. Harrington's and other laboratories have suggested that two distinct types of DNA curvature may be important in specific DNA-protein interactions: sequence directed fixed or intrinsic axial curvature which determines an overall space writhe; and anisotropic axial flexibility associated with specific sequence elements. Dr. Harrington proposes a line of investigations designed to clarify these ideas in terms of specific DNA conformations and structures. These studies will include: (1) systematic studies of putative sites of high anisotropic flexibility using osmium tetroxide adducts and other chemical probes sensitive to open or distorted DNA structures: (2) development of appropriate scanning probe microscopy technologies to visualize these structural features directly; (3) use of other biophysical techniques such as polyacrylamide gel retardation, ring closure (cyclization), fluorescence energy transfer and electrooptical methods to characterize and quantitate DNA curvature; and (4) systematic searches of DNA sequence databases to uncover the biological roles of curving or bending DNA.
