Researchers discover how key enzyme repairs sun-damaged DNA

Jul 25, 2010 by Pam Frost Gorder
Dongping Zhong

Researchers have long known that humans lack a key enzyme -- one possessed by most of the animal kingdom and even plants -- that reverses severe sun damage.

For the first time, researchers have witnessed how this enzyme works at the atomic level to repair sun-damaged .

The discovery holds promise for future sunburn remedies and prevention.

In the early online edition of the journal Nature, Ohio State University physicist and chemist Dongping Zhong and his colleagues describe how they were able to observe the enzyme, called photolyase, inject a single electron and proton into an injured strand of DNA. The two healed the damage in a few billionths of a second.

"It sounds simple, but those two atomic particles actually initiated a very complex series of ," said Zhong, the Robert Smith Associate Professor of Physics, and associate professor in the departments of chemistry and biochemistry at Ohio State. "It all happened very fast, and the timing had to be just right."

Exactly how photolyases repair the damage has remained a mystery until now.

"People have been working on this for years, but now that we've seen it, I don't think anyone could have guessed exactly what was happening," Zhong said.

He and his colleagues synthesized DNA in the lab and exposed it to , producing damage similar to that of sunburn, then added photolyase enzymes. Using ultrafast pulses, they took a series of "snapshots" to reveal how the enzyme repaired the DNA at the .

Ultraviolet (UV) light damages skin by causing chemical bonds to form in the wrong places along the DNA molecules in our cells.

This study has revealed that photolyase breaks up those errant bonds in just the right spots to cause the atoms in the DNA to move back into their original positions. The bonds are then arranged in such a way that the electron and proton are automatically ejected out of the DNA helix and back into the photolyase, presumably so it could start the cycle over again and go on to heal other sites.

All plants and most animals have photolyase to repair severe sun damage. Everything from trees to bacteria to insects enjoys this extra protection. Only mammals lack the enzyme.

Humans do possess some enzymes that can undo damage with less efficiency. But we become sunburned when our DNA is too damaged for those enzymes to repair, and our skin cells die. Scientists have linked chronic sun damage to DNA mutations that lead to diseases such as skin cancer.

Now that researchers know the mechanism by which photolyase works, they might use that information to design drugs or lotions that heal , Zhong said.

Normal sunscreen lotions convert UV light to heat, or reflect it away from our skin. A sunscreen containing photolyase could potentially heal some of the damage from UV rays that get through.

Perhaps ironically, photolyase captures light of a different wavelength -- visible light, in the form of photons -- to obtain enough energy to launch the healing electron and proton into the DNA that has been damaged by UV light.

Researchers knew that visible light played a role in the process -- hence the term "photo" in the enzyme's name -- but nobody knew exactly how, until now.

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xamien
1 / 5 (1) Jul 26, 2010
It raises the question of why we never developed the photolyase enzyme gene ourselves... What did we gain (or avoid) in not developing it?
ettdizzle
4 / 5 (1) Jul 26, 2010
missing an enzyme doesn´t have to be selective. if one whole clade is missing an enzyme that everyone else has it´s likely that their common ancestor simply lost it by chance in a gene deletion or something.

if humans have novel enzymes that perform similar functions but less effeciently, that´s an indication that UV-damage repair gives a strong selective advantage and we´ve evolved enzymes to compensate for the one mammals lost.
vdknockers
4 / 5 (1) Jul 26, 2010
It raises the question of why we never developed the photolyase enzyme gene ourselves... What did we gain (or avoid) in not developing it?

Though it is remarkable to realize the similarities between plant and animals photolyases, it should not come as a huge surprise that humans and other mammals do not express such an enzyme. We as mammals have evolved other qualities for UV defense that have proved sufficient in maintaining our species.

A functional human photolyase application does seem very compelling