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In one direction or the other: that is how DNA is unwound

30 October 2019
Joining computer simulations and lab experiments, an international research group sheds light on one of the key mechanisms of cell life

From home to office and back. The road is the same, and yet the outbound journey is longer than the inbound journey. Why is that? The reason is the obstacles the car driver usually finds on his way to work, which are absent on the way back. Now, replace the road with DNA strands and you will have grasped the crux of the discovery just published by an international research group in the journal PNAS. The double helix of DNA is subject to the action of specific proteins, called helicases, which have the task of separating the two strands so that the information contained in the genome is made available for a variety of activities that are essential to cell life. In short, DNA is like a book, it needs to be opened to be read! Helicases have the task of opening this “book”.

Through this work, the researchers have shown that helicases succeed in carrying out their task more easily, and therefore quickly, working on one of the two strands with respect to the other. They explained that the reason lies in the sequence composition of the DNA section. As we know, DNA has four nitrogenous bases, which constitute the alphabet that is used to write our genome. When there are “hindered” bases like adenine and guanine on the strand opposite to that on which the helicase moves, they bump against the helicase and make the process slower. If, on the contrary, there are “small” bases, like cytosine and thymine, the opening process is faster.

The scientists infer that this could mean that the genome has yet-another way, which has not been considered until now, of regulating the flow of information: indeed, the genetic information connected with the direction in which the helicase proceeds more slowly will be read less frequently – with possible consequences on the gene expression. The research was initially conducted with computer simulations.  The predictions obtained in this manner were then confirmed by experiments. The study emerged from an idea of two SISSA scientists, Professor Giovanni Bussi and Francesco Colizzi, who has since moved to the Institute for Research in Biomedicine (IRB Barcelona), Spain, and has involved the laboratories led by Carlos Penedo and Malcolm White at the University of Saint Andrews, Great Britain, with their collaborators. (Image by Francesco Colizzi)