DNA repair has been captured in a step-by-step molecular movie

Two teams of researchers have uncovered microscopic details of how a protein called photolyase uses light to repair DNA. The discovery could help develop sustainable technologies for chemical manufacture that rely on sunlight.

Most organisms, except many mammals, have photolyase. These proteins repair DNA damage from UV radiation using light. “They’re very good at using almost every single photon they catch,” says Thomas Lane at the German Electron Synchrotron (DESY). “So, for every photon of light, which is the smallest amount of light possible, they can typically generate a DNA repair,” he says.

A DNA molecule comprises two molecular strands that twist around one another, creating a structure similar to a spiral staircase. Each strand has a series of chemical bases along its length, and the bases on the two strands connect up to link the two strands together.

When DNA is damaged, base pairs can break apart. This causes adjacent bases on the same strand to bond together, meaning they can no longer connect to the bases on the opposite strand.

Previous research has shown that photolyase isolates this damaged area and pulls apart the unwanted bonds between adjacent bases, which allows the bases to once again pair correctly with those on the opposite strand. Yet how photolyase achieves this, especially with the high efficiency researchers have observed, remains a mystery.

So, Lane and his colleagues used pulses of high-energy X-rays to create a sort of stop-motion animation that captured the process in atomic detail. Manuel Maestre-Reyna at Academia Sinica in Taiwan and his colleagues conducted a series of similar experiments, which were published alongside those of Lane’s team.

For the experiments, the researchers kick-started the reaction by shining a laser on photolyase in the presence of damaged DNA strands. Then, they delivered X-ray pulses in rapid succession to capture a sequence of images of the arrangement of atoms during the repair process, which lasts about 200,000 nanoseconds.

The researchers found that the area of photolyase responsible for inducing DNA repair, known as the cofactor, initially forms a V shape. Once it absorbs light, it enters a highly energetic state, turning upside down into an inverted V. The rest of the protein stabilises the excited cofactor while it transfers an electron to the damaged DNA. This electron then breaks the bonds fusing the adjacent DNA bases together, one at a time. The electron is subsequently transferred back to the cofactor, which returns to its upward V shape. After the bonds break, the photolyase releases one base first and then the other so they rejoin their base pairs on the opposite strand.

Previous imaging techniques were incapable of observing photolyase repair DNA at this level of detail, says Marten Vos at École Polytechnique in France. Such detailed insights of photolyase’s structure yields clues into how it operates so efficiently, which could help scientists develop similar energy-efficient proteins for manufacturing chemicals and products more sustainably, he says.