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How UV Radiation Causes DNA Mutations

We all know that we are supposed to put on sunscreen in the summer months to protect ourselves from skin cancer, and the connection between sun exposure and cancer is well documented (Koh et al., 1996; Armstrong and Cust, 2017). UV-A and UV-B rays from the sun interact with the DNA in our skin and can cause mutations that ultimately may lead to cancer.

Understanding how UV causes mutations is important in understanding the mechanisms underlying skin cancer, but also in understanding the detrimental effects that UV light can have on our DNA-based experiments. In cells, DNA repair mechanisms can fix UV-damaged bases, but in purified plasmids, no such mechanisms exist, and unrepaired UV damage can be detrimental to the success of downstream applications.

In this article, we outline what you need to know about UV light and two mechanisms by which it can cause mutations: dimerizing mutations and oxidative mutations.

What is UV Light?

Ultraviolet (UV) light is the part of the electromagnetic spectrum between 200 and 400 nm, with shorter wavelengths than violet of the visible spectrum (hence the name, ultraviolet). This range is further divided into short wave (200-280 nm, UV-C), middle wave (280-315 nm, UV-B), and long wave (315-400 nm, UV-A) light. The shorter wavelength UV-C light carries with it a lot more energy than its long wave UV-A counterpart, and is much more damaging to DNA. UV-B and UV-C rays are two types of high-energy radiation that are capable of ionizing (removing electrons from) molecules in a process called a photochemical reaction that leads to new molecular products.

UV damage occurs via two distinct types of mutations:

  1. Dimerizing mutations
  2. Oxidative mutations

Dimerizing Mutations

The most common photochemical product in DNA is a cyclobutane pyrimidine dimer. This product forms when two adjacent pyrimidines (thymines, TT, or cytosines, CC) become linked covalently by their C=C double bonds. These four carbons form a cyclic ring (cyclobutane) that links the two pyrimidines, thus creating a chemical intermediate that is not normally found in DNA. This photochemical product causes a structural kink in the DNA that prevents the pyrimidines from base pairing, and prevents DNA replication.

Oxidative Mutations

UV exposure doesn’t always lead directly to mutations in the DNA. In fact, UV-A radiation commonly causes the creation of a free radical that then interacts with and oxidizes DNA bases. These oxidized bases don’t pair correctly during replication, causing mutations.

One example of this is a G to T transversion mediated by reactive oxygen species. The oxidation of guanine into 8-oxoguanine prevents the hydrogen bonding required to base pair with cytosine. Instead, during replication, 8-oxoguanine can base pair with adenine via two hydrogen bonds. When the second strand is synthesized, the base position originally occupied by a guanine is then replaced with a thymine, leading to a G to T transversion.

Images by Lynnea Waters, constructed with eMolecules®.

What Does This Mean in the Lab?

Well, a plasmid that contains UV-induced dimerizing mutations is unlikely to be replicated efficiently in E. coli. The structural change brought about by dimerizing mutations leaves the plasmid DNA available to repair enzymes. However, errors in repair commonly lead to the replacement of cytosine for thymine, thus changing the original DNA sequence in potentially detrimental ways.

In Summary

Both long and short wavelength UV light are damaging to DNA, but in different ways. Short wavelength UV-B and UV-C light can directly cause dimerization of pyrimidines, and directly prevent replication of plasmid DNA, or induce mutations after faulty repair. Long wavelength UV-A light is generally less directly damaging, and instead causes mutations through the production of reactive oxygen species. In the lab, UV-A is less harmful to naked DNA. This is why it is best to use a long-wavelength transilluminator to visualize DNA bands, if possible! However, with enough exposure, UV-A light could still damage your DNA.

Hopefully this article has not only taught you the importance of using a broad-spectrum sunscreen, but also taught you the chemistry behind the damaging effects of UV light. What other questions do you have about UV light or DNA mutations?

References

    1. Koh HK, Geller AC, Miller DR, Lew RA. (1996) Prevention and early detection strategies for melanoma and skin cancer. Current status. Arch Dermatol 132:436-43.
    2. Armstrong BK, Cust AE. (2017). Sun exposure and skin cancer, and the puzzle of cutaneous melanoma: A perspective on Fears et al. Mathematical models of age and ultraviolet effects on the incidence of skin cancer among whites in the United States. American Journal of Epidemiology 1977; 105: 420-427. Cancer Epidemiol. 48:147-156.
Image credit: earthlydelights

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