Why Looping is Biologically Sensible
DNA looping solves three regulation problems involving DNA. This regulation can be of gene expression, DNA recombination, or DNA replication. The discussion below is couched in terms of gene regula-tion, but the same arguments apply to the other looping situations. The first problem solved is that of space. Most gene regulatory proteins must bind to specific DNA sequences to be able to direct their activities to specific promoters. There may not be room immediately adjacent to a bound RNA polymerase for all the proteins that need to affect transcrip-tion from that promoter. DNA looping provides a solution. A regulatory protein can bind at some distance from an initiation complex and still directly affect transcription by means of DNA looping.
The second problem that DNA looping helps solve is concentrations. This is particularly a problem in eukaryotic cells. Many cell-types have the capability of inducing very large numbers of genes. This means that the relevant regulatory proteins must all be present in the nuclei of these cells. The concentration of any single regulatory protein cannot be high since all the proteins must share the same volume. Therefore the system might try to design the binding sites so that the regulatory proteins bind particularly tightly to the DNA. Unfortunately, such tight-binding could interfere with other cellular operations like replication, repair, and recombination. Nonetheless, systems can be built so that the binding affinity of the proteins for the sites is not too high and yet the binding sites are well occupied. The general method of doing this is to increase the concentration of the protein in the immediate vicinity of its binding site. DNA looping accomplishes this.
The third problem DNA looping solves concerns time. Due to the low concentrations of the individual regulatory proteins that must be main-tained within cells, significant time could elapse until a regulatory protein could find its site and bind. If the protein is already on its site, but kept from activating transcription by looping, then induction can be extremely rapid. It is merely the time required to unloop.
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