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The 2015 Nobel Prize in Chemistry rewards works on the spontaneous degradation of DNA. The study of this spontaneous degradation led to the validation of Imagene technology.
The awarding of the Nobel Prize in chemistry recognizing the contribution of three researchers in the field of DNA repair is important for those interested in the stability – and the conservation – of DNA. While it was known before the 1970s that DNA attacked by physical factors (UV for example) could be repaired in vivo, it was Thomas Lindahl who first suggested that it could be spontaneously damaged, probably by hydrolysis, under physiological conditions, contrarily to the general feeling of the time that the stability of DNA in an organism was such that the integrity of the molecule was guaranteed for life.
However, to validate his hypothesis, he needed to determine the rate of hydrolysis under physiological conditions, particularly at 37 ° C, to show that it was significant at this temperature. But this rate was too slow to be determined. So he placed himself at several elevated temperatures to determine how the rate of degradation varied with temperature. He found that in the temperature range used, this rate of degradation followed the Arrhenius law *.
From these determinations, he was able to determine the rate of hydrolysis at 37 ° C by simple extrapolation. He was thus able to show that, at this temperature, this rate was significant and consequently, in vivo, the maintenance of the integrity of the DNA, necessary for the survival of the organism implied the intervention repair mechanisms, which opened up this field of research.
The use of Arrhenius’s law, though very general, is based on an extrapolation, the validity of which may be challenged in some rare cases. However, in this example, no fact has come to question this validity and many other works by Lindahl and others have confirmed the validity of this approach. Making use of it, Imagene’s work highlighted a very high stability of nucleic acids at room temperature under adequate storage conditions.
* It states that there is a linear relationship between the logarithm of the rate constant of a reaction and the inverse of the absolute temperature at which it occurs, which is graphically represented by a straight line. This allows to obtain the rate of degradation at any temperature, in particular 37 ° C or 25 ° C.
Jacques Bonnet
Emeritus Professor at the University of Bordeaux, Molecular Biologist, Chemist, Co-founder of Imagene