Nucleic Acid Structure, Dynamics and Protein Interaction

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

Because of its structure and variable base composition, DNA is not an isotropic material. The overall objective of this work is to understand how the local properties of DNA depend on its sequence. DNA in cells is folded into higher order structures, whose energetics depend on the local shape and resistance to deformation. Most of the human genome does not code for proteins, but may contain signals for folding and regulatory regions if we could read them. Understanding the variation of DNA flexibility and curvature with sequence should help provide the needed decoding algorithm. The method of DNA cyclization kinetics, using specially designed cyclization constructs in a high-throughput mode, will be used to characterize the properties of specific sequence elements, alone and in complex with ligands such as proteins and sequence- specific polyamides. The sequence-dependence of the dynamic properties of DNA deformation is also poorly understood at present, a deficit that the proposed work will address through the kinetic and dynamic properties of protein and polyamide complexes, with a special focus on cases in which the DNA is bent.