Q6(d). Forces that hold the DNA double helix

Introduction. B-DNA is two antiparallel polynucleotide strands wound into a right-handed double helix: the sugar–phosphate backbones run on the outside and the bases pair on the inside, like the rungs of a twisted ladder. Several weak forces, added together over thousands of base pairs, hold it together.

Figure: Sketch: two antiparallel backbones; A=T linked by two hydrogen bonds, G≡C by three (dashed); base pairs stack along the axis.

1. Hydrogen bonds between base pairs (Watson–Crick pairing): adenine–thymine by two N–H…O/N bonds, guanine–cytosine by three. They fix the pairing (complementarity) and add stability; GC-rich DNA melts at a higher temperature.
2. Base stacking: the planar aromatic bases stack on top of one another, slightly rotated; van der Waals attractions between the mutually induced dipoles of adjacent pairs are individually weak but, summed, contribute significantly to stability. Stacking is strongest between purines.
3. Hydrophobic effect: the relatively non-polar bases are buried inside the helix, away from water; this reduces their exposed surface and increases the entropy of the surrounding water.
4. Hydration and ionic interactions: the phosphodiester groups are ionised (negatively charged) at physiological pH and are placed on the outside, in contact with water; counter-ions (Na⁺, Mg²⁺) screen the repulsion between phosphates of the two strands. In low salt the strands repel and the melting temperature falls.
5. Covalent backbone: 3',5'-phosphodiester bonds hold each strand together; the absence of a 2'-OH makes DNA far more resistant to hydrolysis than RNA.

Conclusion. The double helix is held by inter-strand hydrogen bonds (A=T 2, G≡C 3), base stacking and the hydrophobic effect, helped by hydration and counter-ion screening of phosphate repulsion; covalent phosphodiester bonds hold each strand.

Application. Heat or alkali separates the strands (denaturation, melting temperature) and they re-pair on cooling; this is the basis of PCR and of DNA hybridisation probes.