Scientists focus on single molecules for first time

A team of Cancer Research UK scientists in Scotland is the first in Britain to use a revolutionary technique to study the shape and movement of individual molecules of DNA.

By collaborating with the US team who developed the system – called single molecule fluorescence – researchers have gained the most precise information yet about the workings of single DNA molecules – measuring just one millionth of a centimetre across.

Publishing their results in February’s Nature Structural Biology, scientists describe the intricate processes that occur when tiny pieces of DNA are swapped over during gene repair – a process vital for keeping cancer at bay.

The new technique – developed by scientists at the University of Illinois – works by tagging a molecule with fluorescent chemicals. By analysing the light that these emit, scientists can build up a picture of how the molecule moves, interacts with those around it and performs its biological functions.

Scientists from the Cancer Research UK Nucleic Acid Research Group at the University of Dundee used the system to study a process called DNA recombination, in which cells patch up their genes by swapping a damaged piece of DNA for an intact piece.

Their study reveals that helical strands of DNA swivel round each other in an elegant, dance-like motion, in order to cross over each other in an X-shape. One arm of the X – containing the damaged section of DNA – is then swapped for the opposite arm.

Professor David Lilley, of the Cancer Research UK Nucleic Acid Research Group, says: “It’s incredibly exciting to be using this new technique. For the majority of my career, the smallest things we could study were groups of a trillion molecules simultaneously, thereby losing lots of important detail. Now we can focus in on single molecules, giving us a wealth of information about their individual characters.

“Molecules are not stationary objects – they are dynamic. Like miniature machines, their functions depend on their moving parts. What this technique allows us to do is look in detail at the way that molecules change in shape and orientation as they go about performing their biological tasks.”

While some of the details of DNA recombination were known, the new study has given scientists their most accurate information yet about the process. Since cancer develops as a result of the accumulation of genetic damage, understanding how cells normally repair their DNA is an important area of research into the disease.

The new technique is also likely to prove valuable in many other areas of biology, as science increasingly focuses on the tiny molecules which carry out the functions of life.

Sir Paul Nurse, Chief Executive of Cancer Research UK, says: “There are trillions of cells in our body and in each cell, there are many trillions of molecules, yet it takes errors in just a handful of molecules of DNA for cancer to develop. It’s incredible that we can now take the extent of our vision right up to the level of these incomprehensibly small particles.”

ENDS