A topological twist in DNA melting

Snapshots of typical DNA configurations

Topology plays a key role in biophysics, from genome organisation to cellular motion. Our work suggests a new role in DNA melting.

When a double-stranded DNA helix is heated up, the H-bonds keeping the double helix together break, and DNA melts into two single strands.  Long ago, experiments revealed that DNA melting in circular DNA is much smoother than in linear DNA.  Why is this the case?  Most theories attempted to identify a mechanism turning the abrupt, first-order transition of linear molecules into a smooth, second-order one.  Our simulations led us to an alternative explanation, based on the fact that circular DNA needs to conserve the linking number between its two strands.  

Instead of a traditional transition between zipped and melted state, increasing the temperature takes the system into a coexistence region between a denaturation bubble of unlinked single-stranded DNA, and a double-stranded phase where the DNA linking lost in the bubble is stored as writhe (so the double-stranded section looks like a coiled up phone cord).  This coexistence region can extend over a wide temperature range, with the DNA fraction in the bubble and double-stranded phases varying gradually with temperature, which may account for the experimental results.  Our results suggest new single molecule experiments to be performed on topologically-constrained DNA melting.

Dr Davide Michieletto reported "Topology plays a key role in biophysics but its understanding is often limited by the lack of a suitable theoretical framework.  In this work we have managed to put together theory and simulations to give a qualitative description of how topology affects DNA melting that explains existing experimental observations."