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By Ryan Hopkins
It's about the time of year in the northern hemisphere that we start to notice the days becoming longer and the sun starting to show the overcast of winter. There is still much of winter left to get through, but soon enough the warmth and sun will be back in full. The return of the sun means more time outdoors, but it brings with it the much less enjoyable ultraviolet rays. UV rays can cause damage to our skin ranging from a light tan to sunburn to harmful skin cancers. This is something we are all aware of, but how exactly does it happen? How ultraviolet light reacts in cells is a fascinating process, and I hope understanding it will give you something interesting to think about before going back into the sun this spring!
One way ultraviolet light can harm cells is by directly damaging DNA. This is something many of us are reminded of every spring and summer - it's the cause of sunburn! As the name suggests, direct DNA damage occurs when a photon of UV light hits DNA. DNA is a very large molecule that normally absorbs the energy it gains when hit with a photon of UV light and then quickly releases that energy as heat. During the time after the DNA absorbs the energy and before it dissipates the heat, it is in a higher energy state and is more reactive; the shorter this reactive time is, the less likely it is that the DNA will undergo a harmful reaction. It turns out that DNA is extremely effective at dissipating the extra energy quickly, so it gets damaged less than .1% of the time it's hit by UV light. In the cases where damage does occur, how does it happen? There are different ways excited DNA can react, but the fusing of two base pairs is the most common. If two pyrimidine base pairs (thymine or cytosine) are next to each other, the two rings can fuse together. This type of reaction, called a pericyclic reaction, is possible because of how close the rings are and how their symmetries align. The formation of a four-carbon ring between the pyrimidines makes it difficult for DNA replication enzymes to determine what base pairs should be across from the fused pyrimidines. A copying mistake like this can change how the DNA encodes a protein, resulting in an abnormal protein. If the mutation occurs in an area which codes DNA repair enzymes or tumor suppressing proteins, this mutation could lead to cancer.
Ultraviolet rays can also damage DNA indirectly. How? The story starts with melanin, a class of compounds which organisms produce that
Occasionally, this protection doesn't work as intended. Ultraviolet radiation can either cause melanin to react or hit a molecule which isn't built to dissipate the energy, like an amino acid. When this happens, the excited molecule can excite an adjacent oxygen atom, turning the stable molecule into a reactive species. Oxygen is much less stable in its excited, higher energy state, so it will react with any proteins or lipids it collides with in the cell in order to go back to its more stable, lower energy state. Although it can damage various molecules in the cell, the most damage occurs when it hits DNA. When an excited oxygen hits DNA, it can cause a guanine to thymine transversion, which means that the purine guanine is replaced by the pyrimidine thymine. As in the case of direct DNA damage, this mutation alters how the DNA is translated into a protein and can be potentially harmful. Part of what makes this type of DNA damage particularly dangerous is that it is caused by excited oxygen molecules, not the UV light itself. Excited oxygen has an unusually long lifespan for a reactive species, so the damage can occur in cells other than skin cells.
Damage can also arise if the excited oxygen collides with a molecule of hydrogen peroxide - the same compound in household disinfectant. Hydrogen peroxide is produced in the mitochondria as a by-product of cellular respiration. The cell usually turns the peroxide into water, but some molecules escape this process. If an excited oxygen hits hydrogen peroxide, the peroxide splits in half and forms two hydroxyl radicals. Hydroxyl radicals are a hydrogen atom bonded to an oxygen atom with an unpaired electron (this is what makes it a radical). Electrons always prefer being in pairs, so having an unpaired electron makes a compound very reactive. The hydroxyl radical can attach to the backbone of DNA (deoxyribose), which can cause the DNA strand to break or a base pair to be released. Both of these outcomes can be very harmful to the DNA or the cell.
Our bodies, however, do not lie down and accept their fate - there are numerous defense mechanisms to protect against and mitigate the damage. When direct DNA damage fuses two base pairs together, the DNA has a bulge in its normal double helix shape. Several enzymes travel around the DNA looking for this abnormality. When they find such a bulge, they activate repair proteins that cut out the damaged part of the DNA and put in the correct base pairs. This whole process is called nucleotide excision repair. The effect of indirect DNA damage is harder to detect because transversion does not result in a distorted helix. The mechanism that repairs this kind of damage is called base excision repair. Enzymes called DNA glycoslase remove a base pair misplaced by transversion; other enzymes then open up the DNA's backbone so that DNA building enzymes can come through and fill the gap with the correct base pair. Our bodies have mechanisms that help us in the long-term as well. Direct DNA damage signals the production of additional melanin, so that the next time the skin is exposed to UV light, more can be harmlessly absorbed by the melanin. This means that anytime you become more tan after being outside, there was direct DNA damage! So give your DNA a break and apply sunscreen the next time you're enjoying the sun!
Note: I drew the pictures, so if you see any errors or would like another reaction displayed, please comment!
Agnez-Lima, Lucymara F., Julliane T.a. Melo, Acarízia E. Silva. "DNA Damage by Singlet Oxygen and Cellular Protective Mechanisms." Mutation Research/Reviews in Mutation Research 751.1 (2012): 15-28. Web.
Loft, S., A. Astrup, and H. E. Poulsen. "Oxidative DNA Damage Correlates with Oxygen Consumption in Humans." The FASEB Journal 8.8 (1994): 534-37. University of Chicago Science Library. Web.
Setlow, R. B. "Cyclobutane-Type Pyrimidine Dimers in Polynucleotides." Science 153.3734 (1966): 379-6. Web.
Parrish, John A., Kurt F. Jaenicke, and R. Rox Anderson. "Erythema And Melanogenesis Action Spectra Of Normal Human Skin." Photochemistry and Photobiology 36.2 (1982): 187-91. Web.
