New Look At DNA Hints At Origin Of Ultraviolet Damage

Inthe current issue of the journal Nature, Bern Kohler and his colleaguesreport that DNA dissipates the energy from ultraviolet (UV) radiationin a kind of energy wave that travels up the edge of the DNA molecule,as if the energy were climbing one side of the helical DNA “ladder.”

The finding lends insight into how DNA damage occurs along the ladder's edge.

Italso counters what scientists proposed in the 1960s: that UV causesmutations by damaging the bonds between base pairs – the horizontal“rungs” on the ladder. The new study shows that UV energy movesvertically, between successive bases.

In undamaged DNA, there areno chemical bonds between vertically stacked bases. But the bases dointeract electronically, which is why Kohler thinks they form anefficient conduit for UV energy to flow through.

“Even thoughpaired bases are connected by weak chemical bonds, it's theinteractions that take place without chemical bonds – the interactionsbetween stacked bases – that are much more important for dissipating UVenergy,” Kohler said.

The Nature paper builds on work from fiveyears ago, when the associate professor of chemistry and his team firstdiscovered that single DNA bases convert harmful UV energy to heat toprevent sun damage in the same way that sunscreen molecules protectsunbathers.

Back then, they studied only single bases floating inwater. They hit the bases with a kind of UV strobe light, and saw thatthe energy was released as heat in less than one trillionth of a second.

Theirnew experiments show that the behavior of full DNA differs profoundlyfrom that of isolated bases. When the chemists turned their strobelight on whole strands of novel DNA, the UV energy still changed toheat eventually, but the energy dissipated a thousand times more slowly.

That'san eternity in the DNA universe, where scientists need to use specialequipment just to see these ultra-fast chemical reactions happen. Yet,Kohler's team saw no evidence that the UV affected the chemical bondsbetween the base pairs. They surmised that the UV energy was leavingthe molecule by traveling along the edges instead.

“This slowrelaxation of energy is utterly different from the mechanism in singlebases that transforms the energy into heat in less than a trillionth ofa second,” Kohler said.

“Eventually, the energy does turn intoheat, but the important point is that the energy is retained within themolecule for much longer times,” he added. “This can cause all kinds ofphotochemical havoc.”

It could be that when base pairs arealigned in their natural state in a DNA strand, the electronicinteractions along the stack provide an easier way for DNA to riditself of UV energy, compared to passing the energy back and forthbetween the two bases in a base pair as scientists have previouslythought.

In fact, it was the brilliance of James Watson andFrancis Crick's discovery of the structure of DNA that kept this secrethidden for so many years, Kohler said. Their work revealed that the DNAhelix was composed of paired bases, and that discovery led researchersto focus on how UV energy might interact with base pairs.

“Infact, so much attention has been paid to base pairing that this otherinteraction, base stacking, has been neglected,” Kohler said.

Basestacking is frequently overlooked, he admitted, because the ladderterminology that we use to describe DNA structure makes us think thatthere are open spaces between successive rungs of base pairs.

A better analogy would be a stack of coins, he said. Bases are stacked right on top of each other.

Here'swhat he and his team suspect is happening during the UV energy wave: assunlight warms our skin, UV photons are absorbed by the bases, causingtheir electrons to vibrate. These high-energy vibrations nudge theatoms in the bases around, but only along one edge of the DNA ladder ata time.

If all goes well, the DNA returns to normal after theenergy wave passes. But some of the time, the atoms don't return totheir original positions, and new chemical bonds are formed.

Scientistsknow that such accidental bonds create “photolesions” – injuries thatprevent DNA from replicating properly. The details of the processaren't fully understood, but studies suggest that photolesions causegenetic mutations that lead to diseases such as cancer.

This new research helps explain why most photolesions are formed between bases on the same side of the DNA strand.

Scientistsbelieve that proteins in the body repair DNA by removing photolesionsand filling in new material, using the remaining DNA strand as atemplate.

If UV damage is confined to one side of the DNA doublehelix or the other, then the undamaged side makes an easy template forthe proteins to follow. But if both sides of a strand were damaged,then the template would effectively be missing.

The Nature paperhighlights the shortcomings of previous studies, which applied resultsfrom isolated base pairs to the full DNA molecule. “It turns out thatyou can't extrapolate the results of base pairs to whole strands ofDNA,” Kohler said.

The discovery has clear implications for biology, since it can help explain the DNA repair process.

“Theability to observe what happens to electronic energy in DNA on suchshort time scales also extends the hope that methods such as ours canfinally determine how DNA is damaged by UV light in the first place,”Kohler said.

The Ohio State chemists are now testing other DNAstrands. For simplicity, they first wanted to compare the behavior ofsingle Adenine and Thymine bases with strands entirely composed ofthose two bases. That is the work described in Nature.

Kohler'steam includes Carlos E. Crespo-Hernández and Boiko Cohen, bothpostdoctoral researchers in the Department of Chemistry at Ohio State.Their work was sponsored by the National Institutes of Health and theAlexander von Humboldt Foundation, and was performed at Ohio State'sCenter for Chemical and Biophysical Dynamics, which is funded by theNational Science Foundation.