Information Encoded in the Sequence-Dependent Mechanics of DNA

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Project 1 investigates a novel kind of genetic information that is encoded directly in the genomic DNA sequence, through the sequence-dependent mechanical properties of DNA itself. This information is superimposed directly on top of protein coding and regulatory signals that were previously recognized, and is based on the sequence-dependent mechanical properties of the DNA itself. Genomes can use this information to tune the stability of protein-DNA complexes containing such sharply distorted DNA through constraints on the detailed DNA sequence, even when these DNA sequences are not contacted directly by any proteins. The degeneracy of the genetic code, and of many DNA binding regulatory proteins' target sites, allow this novel sequence-dependent mechanical information to be superimposed, or multiplexed on top of other kinds of genetic information without distortion or cross-interference. Examples of essential biological structures in which DNA is sharply distorted in this way include eukaryotic nucleosomes (in which 75-90% of all eukaryotic DNA is organized), and also many double-strand DNA- (dsDNA-) containing viruses, and many bacterial and eukaryotic protein-DNA gene regulatory complexes. Project 1 combines theoretical and experimental approaches to develop a predictive mechanistic understanding of these fundamentally important sequence-dependent mechanics of DNA.