Spring Break means warmer weather and the allure of sunny beaches. But while sun-loving students head out to beaches every spring to enjoy sand and surf, ultraviolet rays could be damaging their skin’s genetic code and causing skin cancer, the most widespread cancer in North America.
Future generations of spring beach-goers will be pleased to know that Ohio State University scientists are making progress towards understanding why certain DNA sites are much more susceptible to UV damage than others.
Researchers already know that certain points in the genome are damaged by UV rays much more readily than others, but Bern Kohler, an Ohio State professor of chemistry, and Yu Kay Law, a graduate research associate in biophysics and Kohler’s advisee, hypothesized that the structure or shape of a skin’s DNA molecule at the time it absorbs UV light determines whether or not the DNA will be damaged.
The double-helix form of DNA constantly fluctuates, undergoing many billions of subtle, yet distinctive, structural changes every second as it gets jostled by water and other molecules within cells, according to Kohler.
“Because we know the cell’s DNA is dynamic, and motions such as helix bending or stacking and unstacking of bases occur relatively slowly, we suspected that the most typical type of damage created by UV light, cyclobutane pyrimidine dimer, form only when conditions are just right,” said Law. CPD damage interferes with normal cell processing of DNA, which can lead to mutations that cause diseases such as cancer.
“Damage is a rare event, because most of the time DNA is found in structures that are damage-proof,” Kohler explained. “However, a small fraction of the time DNA molecules find themselves in the wrong place at the wrong time … .”
Using the supercomputers at the Ohio Supercomputer Center to conduct data-intensive molecular dynamic simulations, Kohler and Law investigated the many millions of different shapes DNA takes on as it fluctuates in water and various organic co-solvents. In research that is slated to be published in the April issue of Biophysical Journal, they verify that CPDs are created only when adjacent thymine bases of DNA are favorably aligned and in an excited state from the energy provided by UV light.
“Advanced technology is vital to this research; without the use of supercomputers, we would only be able to speculate on the mechanisms of UV damage,” Law said. “These results are significant because they reveal the shapes that make DNA vulnerable to damage and help explain why CPDs are formed more readily at certain sequences. This insight allows us to advance our studies and investigate ways by which these mutations are controlled in living organisms through sequence variation and protein binding.”
Biophysical Journal article available now online at http://dx.doi.org/10.1529/biophysj.107.118612
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