Film shows how light repairs DNA damage

Ultraviolet radiation, such as that found in sunlight, attacks the genetic material and causes damage to the DNA. “Damage of the so-called CPD type occurs most frequently,” explains Lars-Oliver Essen from the Philipps University of Marburg, one of the lead authors of the study DNA strands can no longer be read at these points.” CPD damage is the main cause of sunburn and skin cancer in humans.

But light can not only destroy DNA, but also help to eliminate the errors that have arisen. Photolyase enzymes obtain energy from blue light to eradicate the CPD damage caused by ultraviolet radiation. “Photolyases offer protection against UV radiation to almost all living beings that are exposed to the sun,” says biochemist Professor Dr. Ming-Daw Tsai of National Taiwan University, another lead author.

Essen has been working on this type of light-driven enzymes for a long time: “For example, 20 years ago we discovered the structural peculiarities to which photolyases owe their unusually high efficiency for DNA repair,” says the chemist.

Technical breakthroughs of the last ten years are helping to elucidate the structure of large molecular complexes:

On the one hand cryo-electron microscopy, on the other hand time-resolved serial femtosecond crystallography. “The main advantage of cryo-EM is its ability to display very large complexes with high resolution,” explains Essen. “Femtosecond crystallography, on the other hand, makes it possible to monitor in real time how the structure of light-sensitive macromolecules such as photolyases and the DNA bound to them changes.”

Essen brought together experts from all over the world to use the new methods to elucidate the mechanism by which photolyase repairs CPD damage. “We took 18 snapshots at different points in time, which ensure a temporal resolution down to the range of 100 picoseconds, i.e. a ten-billionth of a second,” says Essen’s former employee Dr. Manuel Maestre-Reyna, who now holds a professorship at the National Taiwan University and is the first author of the study.

DNA photolyases and their repair mechanism

“Now, for the first time in the film, you can see how the DNA repair enzyme breaks one faulty bond after another on the CPD damage before it detaches itself from the DNA once the work is done,” explains Essen. “Our data now covers the complete molecular mechanism of one of the most widespread DNA repair systems,” emphasizes the biochemist. “The results represent a culmination of my long-standing interests in DNA photolyases and their repair mechanisms.”

Lars-Oliver Essen teaches biochemistry in Marburg. In addition to his working group and colleagues from Taiwan around Maestre-Reyna and Tsai, head of the Taiwanese protein project, numerous experts from Japan, Switzerland, France, the USA and Italy took part in the study. The German Research Foundation and numerous funding organizations from Taiwan, Japan and the USA financially supported the underlying research work.

Those: Philipps University of Marburg

Originalpublikation: Manuel Maestre-Reyna et al.; Watching the entire DNA repair process by a photolyase at atomic resolution in real time; Science2023; DOI: 10.1126/science.add7795