Ohio State chemists have taken an important step in understanding the causes of skin cancer.
Bern Kohler, associate professor of chemistry, teamed up with research associates Carlos Crespo-Hernandez and Patrick Hare to probe the an unusual, dark, excited state of DNA for the first time.
“Ultraviolet light is absorbed strongly by the bases, A, G, C and T, which encode the genetic information stored in DNA,” Kohler said. “The energy deposited by ultraviolet light sometimes leads to chemical modification of the bases. These modifications can result in mutations, which can in turn trigger diseases like skin cancer.”
Kohler’s research group, which has been studying excited states in DNA since the late 1990s, is dedicated to understanding how ultraviolet light causes DNA damage.
“The results are significant in understanding DNA photophysics and photochemistry and have a broad impact in DNA field,” said Dongping Zhong, assistant professor in physics, chemistry and biochemistry, whose research on ultrafast proteins is similar to Kohler’s work.
DNA contact with ultraviolet light causes electrons to be in an agitated state. The excess energy can either lead to a photochemical reaction or it can simply be dissipated as heat.
“You can think of an excited state kind of like a skier at the top of a mountain,” Kohler said. “The ski lift has increased your energy substantially, just like the ultraviolet photon absorbed by a DNA base. At the top of the mountain, you can take any of several ski trails. Most of them will return you to the lodge at the base of the mountain, or back to your initial state in the same way that most DNA excited states decay without altering the molecular identity of the bases.”
Kohler said the excited state decay pathways in DNA that lead to photo damage are the equivalent of a few trails that lead somewhere else and never return to the starting point.
“In the language of this analogy, our recent work has identified a second trail that is unique to those bases, which are damaged most often in DNA,” Kohler said.
The difficulty in this type of research is being able to find reactions that cause chemical modifications.
“The chemical alterations that are so harmful happen less than 1 percent of the time, making it hard to observe these rare events,” Kohler said.
Kohler’s group uses a technique entitled pump-probe transient absorption spectroscopy.
“An initial laser beam, the pump excites the DNA bases while a second pulse, the probe beam measures the evolution of the high-energy states that result from the ultraviolet excitation,” Kohler said.
This research also has shed some light on the possible beginnings of life on Earth.
“The idea that DNA is more resistant to ultraviolet damage than other molecules also explains how life could have gotten started on the early earth, where ultraviolet levels are thought to have been much higher than today,” Kohler said.
Andrew Kieta can be reached at [email protected].
