Many genetic regulatory processes involve protein-DNA interactions in which the DNA helix is substantially distorted. Moreover, certain sequence arrangements in DNA can give rise to substantial curvature of the helix axis in the absence of protein; this latter phenomenon has also been implicated in several biological process, including replication and the regulation of transcription. In order to understand the mechanisms underlying these regulatory processes, it is essential that the energetic cost of such helix distortions be known on a quantitative level. The focus of the proposed research is therefore to provide such a quantitative picture. The proposed research has two principle objectives: (i) to define the extent to which base sequence influences the intrinsic rigidity of DNA, and (ii) to further characterize the properties of intrinsically curved DNA. Our main experimental approach will be that of DNA ligase-catalyzed ring- closure, using methodology developed in our laboratory during the previous period of funding.
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