February 19, 2015
The damage the sun inflicts on your skin may be even more insidious than was previously thought, according to new research.
A study published Thursday in Science finds that the effects of sun exposure can continue to wreak havoc on your DNA — even in the dark.
The researchers say that as much as half the harm the sun does to the DNA in skin cells occurs up to three hours after exposure via a chemical process they call the “dark pathway.”
“The main lesson of our research is that your skin doesn’t stop getting damaged when you get out of the sun,” said Douglas Brash, professor of therapeutic radiology and dermatology at Yale School of Medicine and the senior author of the paper.
Scientists have known for 50 years that exposure to UVB and UVA light negatively affects the DNA in skin cells. When a photon is absorbed by DNA, it can cause the bonds of two of the base letters on the DNA strand to fuse together. This puts an unnatural bend in the DNA and makes it difficult for it to replicate properly.
This type of damage is called a cyclobutane pyrimidine dimer (CPD) and it happens in a millionth of a millionth of a second — right after the photon hits the skin.
“It should be the end of the story,” Brash said.
But in 2011 Brash and Sanjay Premi, an associate research scientist in therapeutic radiology at Yale, made a surprising discovery. They had just received a grant to study human and mice skin cells called melanocytes that produce melanin. Specifically, they planned to study how those cells respond to UV exposure.
To make sure all their lab equipment was working correctly, the researchers exposed the cells to UV light and then measured the number of CPDs or dimers that occurred.
When they looked at the samples again a few hours later, they expected to see the amount of dimers would go down thanks to the repair mechanisms in cells, but instead, the number had increased.
“The first time we did this, we thought it was a defect,” said Premi. “But we replicated it several times, using different techniques to confirm this was the real thing.”
Once the researchers determined that UV exposure really was continuing to harm DNA even after the lights went out, they decided to figure out why.
In a series of experiments they found that direct exposure to UV light causes dimers to occur in the DNA of all types of skin cells, but only melanocytes continued to accrue these defects in the absence of light.
That was another curve ball because melanin is known to protect the skin from direct sun exposure, but now it seemed to be the source of the dark pathway damage.
After more experiments the scientists discovered that UV light activates enzymes in the cell that combine to “excite” an electron in melanin. The energy from this excited electron gets transferred into the DNA. That in turns creates the same damage caused by direct absorption of a photon by the DNA.
Brash said that the chemistry underlying the “dark pathway” has been seen in jellyfish and fireflies, but never before in mammals.
For example, fireflies use the energy of excited electrons to generate bioluminescence, he said.
The dark pathway probably starts during sun exposure, but continues for hours afterward, Brash said.
Now that scientists know about this newly discovered chemical pathway to DNA damage, they may be able to interfere with it. During their research, the scientists used two chemicals that could stop dimers from occurring after UV exposure, and they might give scientists a clue to what types of chemicals to investigate.
“The idea would be to take the energy of the electron and divert it somewhere else,” Brash said.
He said that in the future people might put sunscreen on before they go out and put on another cream during the car ride home.
John-Stephen Taylor, a bio-organic chemist at Washington University in St. Louis, Mo., who was not involved in the study, said the work is impressive.
“To uncover this thing took a range of experiments across a variety of disciplines,” he said. “They did biological experiments and chemical experiments and photo-physical experiments.”
He said that the researchers were not able to see the chemical reaction that led to the DNA degradation firsthand, but that the circumstantial evidence presented in the paper is very convincing.
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