The B-Z Transition Explained: A Case Study In The Electrostatics Of Nucleic Acids
It has been said that biology makes no sense except in the framework of evolution. What then is the evolutionary sense of trusting the genetic information to a highly charged polyelectrolyte? An answer to this question will require an understanding of the electrostatics of nucleic acids. As a case study, we present a unified electrostatic theory of the widely diverse effects of cations on the B-Z transition of DNA.
We showed earlier that the B-Z transition of poly[d(G-C)]. poly[d(G-C)] in high sodium or magnesium is explained by the lesser electrostatic free energy of B-DNA, due to better immersion of the phosphates in the solution. This property was incorporated in cylindrical DNA models which were analyzed by Poisson-Boltzmann theory. The results are insensitive to details of the models, and in fair agreement with experiment.
In contrast, very small concentrations of magnesium are sufficient for stabilizing the Z form of the poly[d(G-m5C)] duplex. We now show that this striking difference between the two polymers is accomodated quantitatively by the same electrostatic theory, without any adjustable parameter (1). The different responses to magnesium of the methylated and non-methylated polymers do not come from stereo-specific cation-DNA interactions: they stem from a modest difference in the non-electrostatic component of the free energy difference (or NFED) between the Z and B forms. The NFED is derived from prior measurements of the B-Z transition in circular DNA. As regards differences between the effects of alkaline earth and transition metal ions (both divalent) they are explained by weak coordination of the latter.
The theory also explains the induction of the transition by micromolar concentrations of cobalt hexammine, again without specific binding or adjustable parameters.
Hence, in the case of the B-Z transition as in others (e. g. the folding of tRNA and of ribozymes), the effect of multivalent cations on nucleic acid structure is mediated primarily by non-specific ion-polyelectrolyte interactions. We propose this as a general rule for which convincing counter-examples are lacking.
M. Guéron, J.-Ph. Demaret and M. Filoche, Biophysical Journal 78, 1070-1083 (2000).
M. Guéron(a), J.-Ph. Demaret(b), and M. Filoche(c)
(a)Groupe de biophysique de l'Ecole polytechnique et de l'UMR 7643 du CNRS,