Part F: A Closer Look at....

Biological Consequences of Ultraviolet Exposure

Why is UV bad for your health?
Some UV is necessary for good health. We can only make vitamin D when solar UV stimulates our skin. Otherwise, we have to add it to our diet. However, most UV, especially the more energetic photons of UV-B, causes harm. These photons damage our cells and organs by producing chemical changes in important molecules, especially proteins and nucleic acids. The lens of the eye is particularly vulnerable. UV absorbed in the lens proteins contributes to the formation of cataract, which decreases the ability of the lens to transmit light, resulting in partial or complete blindness. Exposed skin is subject to short-term effects such as sunburn and longer-term effects such as skin cancer and premature aging. The more we are exposed to UV, the more we risk.
The long-term effects of UV on living things are caused by changes in the genetic material, DNA. Large doses of UV may kill a cell outright by creating too much damage in its DNA. Smaller doses may have lasting effects by causing mutations (changes in the DNA sequence) or recombination between DNA molecules. Genetic changes such as mutation or recombination can affect the growth of cells, in some cases, leading to uncontrolled growth or cancer.

Interaction between UV and DNA

Although UV photons of different energies have various effects on DNA, the most important damage to DNA is the formation of pyrimidine dimers. In the pyrimidine dimer, two adjacent pyrimidine bases--cytosine (C) and/or thymine (T)--are linked in an abnormal structure (Figure 1A & B) which distorts the shape of the DNA double helix (Figure 2) and blocks its copying by the DNA replication or RNA transcription machinery. A block in either of these important processes would be very dangerous for a cell; as little as one dimer per cell in fact, can be lethal. Dimers are formed in DNA most efficiently by UV-C, less efficiently by UV-B, and very little by UV-A action.
How cells suffer from and repair pyrimidine dimers is our primary concern, but UV damages DNA in other ways. Another alteration of the pyrimidine bases, called the 6-4 lesion because of how the molecule is damaged (Figure 1C), may cause mutations. Other types of base damage may also occur, but they are not as biologically important as the dimer or 6-4 lesion.

Repair of DNA damage

Cells of all types have evolved mechanisms for repairing DNA damage. These repair systems deal with damage caused by UV, ionizing radiation, chemical agents in the environment, and just plain everyday wear-and-tear or spontaneous damage. Scientists have found a surprising similarity in the DNA repair systems of fairly unrelated organisms. This similarity, or evolutionary conservation, as a scientist would describe it, tells us two things:
1) repair systems are so important to organisms of all sorts that they changed little through evolution AND must have arisen early in the history of life on Earth;
2) we can use "model" organisms to do experiments that would be difficult to do in larger organisms like people. We use the model organism bakers' yeast here; yeast is a eukaryote like plants, animals, and humans, but grows as a single cell like bacteria and so is easy to cultivate. Working with yeast enables you to take advantage of many years of research other scientists have done on DNA repair processes in this simple organism. Research suggests that DNA repair processes in humans are very similar to DNA repair in yeast.

Another clue to the importance of DNA repair is that most living creatures have developed four different repair processes.
1) Photoreactivation (PR) uses visible light as an energy source to "un-dimerize" pyrimidine dimers.
2) Excision repair makes use of several enzymes to remove dimers and resynthesize DNA.
3) Error-prone repair is yet another enzymatic process that removes dimers, but also makes mistakes, which become mutations in the surviving cells.
4) Recombinational repair occurs when recombination between DNA molecules rescues cells that have developed gaps when DNA that contains dimers is replicated.

The fate of an irradiated cell

What happens to a cell which has been exposed to UV depends on a number of things. If the yeast cell is growing on a grape leaf in the sunshine, it can use photoreactivation to rapidly and accurately repair dimers. The excision repair system is also quite efficient and may find the dimer and fix it first. If DNA replication is occurring and the dimer is in a region of DNA due to be replicated, a mutation might occur if the polymerase tries to copy the dimer instead of stopping; alternatively, if it stops and starts again later leaving a gap, recombination will be required to repair the gap. You can think of the outcome as being dependent on a race between the replication machinery and the different repair proteins. Most of the time, the repair proteins (photoreactivation or excision) win, since even in UV-irradiated cells, mutation and recombination frequencies are low.
A cell will die if a dimer is not repaired. A cell will live and be unchanged if an error-free system repairs the dimer. A cell will live and may be changed if an error-prone or recombinational system repairs the damage. If the change (mutation or recombination) alters an important gene, the cell may die even though the dimer was repaired. In some experiments you can make use of mutant yeast strains that have lost the ability to carry out several of the repair processes. As you would expect, these strains are more sensitive to the UV radiation in sunlight, which makes it easier to do experiments with them.

To Learn More...

Read Repair of DNA

Figure 3-1:

Figure 3-2

Connections Between Ozone and DNA Damage

To see how it all fits together, consider two more kinds of spectra. One is called the absorption spectrum for ozone and the other is the action spectrum for damage to DNA. Recall that a spectrum is a graph of any property plotted against wavelength (or photon energy). An absorption spectrum for something like ozone, then, would be a graph of how well it absorbs photons plotted against the wavelength (See Figure 3). Notice that where the ozone absorption is greatest, the difference between the solar UV and the surface UV is also greatest. 300 DU of ozone effectively absorbs all the UV-C, more than half of the UV-B, but very little of the UV-A.
Now look at the curve in Figure 3 labeled "DNA Action." This curve is the action spectrum for DNA damage. Clearly the wavelengths that are most effective at damaging DNA are also strongly absorbed by ozone. That is extremely fortunate for us. However, notice the small range of wavelengths around 300 nm where the DNA action spectrum and the surface UV spectrum overlap. That is the region (labeled "net DNA effect") where the "action" is. Shorter wavelengths of UV would be more damaging to DNA, but they are removed by the ozone. Longer wavelengths get through the ozone, but they do not have much effect on DNA.
More UV-B of shorter wavelengths penetrates to the surface as the ozone decreases. Since these wavelengths are more damaging to DNA than longer ones, the rate of increase of DNA damage increases as the ozone decreases. In Figure 4 the probability that DNA will be damaged is plotted against the ozone concentration. At very low ozone values, the probability of damage would go up catastrophically. The inset shows that in the range of values around 300 DU, the risk of DNA damage increases by 2.5 percent for each 1 percent decrease in the ozone concentration.

To Learn More...

Read Modeling the Effects of Ultraviolet Radiation, see Video tape section: Global Ozone, and explore the UVRISK computer program.

Figure 3: Sunlight, ozone, DNA interactions.

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