The molecular perspective: ultraviolet light and pyrimidine dimers.

we go about our daily activities. Whenever we walk in the sun, ultraviolet light (UV) attacks our DNA, making chemical changes that corrupt our genetic information. Fortunately, the most dangerous UV light never reaches us at all: the ozone in the upper atmosphere absorbs (at least for now) the energetic UVC wavelengths. The longer UV wavelengths, however, do pass through the atmosphere and fall on us. The UVA wavelengths bordering on visible light, which are often used in tanning booths, are not energetic enough to modify DNA bases (although UVA may play an important role in formation of carcinogenic oxygen radicals). However, wavelengths in the intermediate UVB region are long enough to pass through the ozone but still energetic enough to attack DNA. Ultraviolet light is absorbed by a double bond in pyrimidine bases (such as thymine and cytosine in DNA), opening the bond and allowing it to react with neighboring molecules. If it is next to a second pyrimidine base, the UVmodified base forms direct covalent bonds with it. The most common reaction forms two new bonds between the neighboring bases, forming a tight four-membered ring (Fig. 1). Other times, a single bond forms between two carbon atoms on the rings, forming a “6-4 photoproduct.” These reactions are quite common: each cell in the skin might experience 50-100 reactions during every second of sunlight exposure. Fortunately, most of these genetic lesions are corrected seconds after they are created, before they can do permanent damage. Our cells use a process known as “nucleotide excision repair” to identify and remove ultraviolet damage. Dozens of proteins work together to seek out corrupted bases, unwind the local DNA double helix and clip out a segment of about 30 bases around the damage. The normal DNA replication machinery then fills the gap, restoring the DNA to its proper form. Nucleotide excision repair is our sole defense against ultraviolet damage, but other organisms have backup defenses. For instance, the endonuclease shown in Figure 2 simply clips out the damaged base. The placental mammals have lost these additional defenses, perhaps an evolutionary legacy inherited from the earliest nocturnal mammals, which were seldom subjected to the dangers of ultraviolet light. Even today, many rodents show weakened nucleotide excision repair mechanisms. The Molecular Perspective: Ultraviolet Light and Pyrimidine Dimers