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
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.