Sequence Matters: The Influence of Basepair Sequence on DNA-protein Interactions

The sequencing of the human genome, along with the 200-odd other genomes that have been sequenced, does not represent the solution to a puzzle but rather the necessary introduction to a bigger puzzle. That puzzle is how all the 30,000-odd some genes in the human genome are expressed and controlled in a proper sequence for a cell to function. We can hardly address this enormous problem in this brief review, but instead wish to concentrate on one very small but very important aspect of this problem: physical aspects to how proteins are able to achieve base-pair specific recognition. By “physical aspects” we mean that the proteins distort (strain) the DNA helix when they bind, and if this strain is a function of the sequence of the distorted region then the basepair dependent free energy associated with the strain provides a way to discriminate amongst the basepairs.