Researchers design molecular agents that 'hop' between specific sequences the DNA
The ultimate goal is to control the gene expression processes at will
The CIQUS research group led by Prof. José Luis Mascareñas have designed and prepared a peptide-like molecular system that is able to choose between different specific DNA sequences based on external stimuli. This represents the first example of an engineered molecule that can bind to more than one specific DNA sequence according to changes in their environment.
The work, published in the prestigious journal Nature Communications, has been entirely made in the CIQUS (USC) by the PhD students Jesús Mosquera (currently in a short stay at the University of Cambridge) and Adrián Jiménez, also co-directed by Dr. Eugenio Vázquez.
These systems mimic the behavior of natural genetic regulators that decide which gene should be expressed at each time and in each cell, depending on the stimuli they receive. The activation (or deactivation) of genes are essential processes that direct to the behavior and fate of cells, so it can be considered as a fundamental process in the development of living organisms, as well as in the onset and progression of many diseases.
The designed molecule can be activated in response to external signals. Thus, in the presence of a certain type of metal (stimulus A) it is activated and sticks to a particular genetic sequence (genetic Station A), but if a different signal is applied (oxidizing agent, stimulus B), then the molecule is detached from the first sequence and binds to another sequence of the DNA (genetic Station B). Therefore, one could say that those molecules "hop" between the two genetic sequences according to the external stimuli that we applied. While this work is still just a proof of concept, it also provides the basis for future designs of smart pharmacological agents.
www.nature.com/ncomms/journal/v4/n5/full/ncomms2825.html
Representation of a stimuli-responsive dimerization strategy for specific binding to two DNA sites. Depending on the stimuli (red cylinder or blue cube) the molecules interact with different areas of the DNA.