Why is DNA twisted

DNA "overexcited" when stretching

A single molecule of human DNA measures just a millionth of a centimeter in its normal state, but when fully stretched it would be almost a meter long. The secret of this changeability is the double helix of the genetic molecule. But this behaves completely differently than the scientists would have expected: Instead of unwinding while stretching, the spiral "overwinds", as researchers now report in "Nature".

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The typical double helix shape of DNA resembles a twisted “rope ladder” made up of two side strands and the bases as rungs. Their structure and spatial orientation are crucial for conveying and reading genetic information. Scientists at the Lawrence Berkeley National Laboratory headed by Carlos Bustamante have now for the first time tested in an experiment how the helix behaves when it is expanded.

They used a process called “rotor bead tracking” for this. A single DNA molecule is anchored at one end to a surface and a magnetized bead is attached to the other end. This serves as a "handle" for precise and targeted stretching of the double helix. At a point between the two ends, the double strand is biochemically "cut" so that a loose end is created. The researchers attach a plastic ball coated with fluorescent paint, the so-called “rotor”, to which they can track the rotations of the helix. "When we create tension in the DNA molecule, the changes in the orientation of the rotor bead reflect changes in the winding of the lower DNA segment," explains Bustamante.

Overwinding instead of unwinding

Scientists expected the double helix to begin unwinding when stretched. But the result of their experiment was very different: up to a strength of around 30 picoNewtons - a force around a billion times less than that which lets an apple fall to the ground - the rotation of the helix did not decrease, it actually increased. Only above this threshold did the molecule return to "normal" behavior.

This "overturning" while stretching also makes the DNA longer, not shorter. “The over-rotation when stretching indicates that, contrary to popular belief, the correlation between stretching and torsion is negative,” explains Bustamante. “According to this observation, the molecule would also have to get longer if we over-twist it. And we actually found that the molecule elongated by around 0.5 nanometers per revolution when it was over-rotated. "

The researchers explain the cause of this apparently paradoxical behavior using a simple model: an elastic rod that is wrapped with a stiff wire. The material of the rod retains its volume under stress; if it is stretched, its radius is therefore reduced to compensate for it. “This allows the wire to wrap around the length of the rod more often,” says Bustamante. As a result, the torsion increases.

Shedding new light on protein-DNA interactions

This new relationship between elongation and torsion gives valuable insights into the behavior of DNA-binding proteins, among other things. These dock at specific target points on the double helix and, by stretching, bending and twisting, bring the DNA into its compact outer shape, as it is in the chromosomes during cell division, for example.

“We believe that our work sheds light on an old and important problem,” explains the scientist. “In addition to providing a better understanding of the DNA-protein interaction, it also has implications for nanotechnology. For example, the DNA molecule could be used to drive future nanomotors. ”Like the rubber band in old wind-up cars, the torsion of the helix would then provide the necessary energy.

(Berkeley Lab, 08/09/2006 - NPO)

August 9, 2006