A search for “DNA repair” in Amazon’s “beauty” category results in 71 hits that range in price from $15-$700, all claiming to prevent DNA damage or even to repair your DNA. Both scientists and the beauty industry know that as we grow older, our cells accumulate DNA damage while their ability to correctly repair it declines, leading to changes in appearance associated with aging [1], and the beauty industry is taking advantage of this fact. Whether you have commercially defined symptoms of aging or not, the cells in your body have to repair up to one million DNA lesions per day from both environmental and cellular sources [2].
Failure to properly repair DNA damage can influence not only your appearance as you age but also have other detrimental biological impacts, including the development of cancer. Although we frequently associate environmental sources — ultraviolet (UV) light from the sun, chemicals released by cigarette smoke and pollutants, etc. — with DNA damage and cancer, normal cellular metabolism generates chemical byproducts that alter DNA as well. A new study published this month in the journal Nature focuses on the development of a type of skin cancer called melanoma. The authors of this study found that DNA damage triggered by cellular sources (in the absence of UV exposure) contributes to the development of melanoma, and the types of pigments within a cell influence cancer susceptibility [3].
DNA Damage and its Repair
Life could not exist without the assortment of molecular machines that detect DNA damage, repair the defects, and signal to the rest of the cell that there is a problem. DNA contains all of the cell’s genetic information required to create the molecular machines necessary for cellular function. DNA damage can lead to permanent changes, called mutations, in the cell’s instructions for producing these molecular machines. Mutations occur when cells make mistakes during DNA repair or while copying their DNA before cell division. Since mutations are permanent alterations to the cell’s genetic information, all cells that subsequently arise from the mutated cell’s lineage also contain incorrect instructions for producing molecular machines. The accumulation of mutations can eventually lead to cancer.
To understand how DNA damage leads to mutations and how cells repair their DNA, we need to think about DNA as a chemical with a specific structure. DNA is a large molecule composed of repeating subunits called nucleotides. Each nucleotide consists of two parts: a “backbone” and a base. The nucleotides are strung together through their backbones, and two of these strands wind around each other to form a double helix.
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Just as we can read a sequence of individual letters as a word, cells can read the order of individual nucleotides on a strand of DNA to produce functional molecular machines called proteins. The region of DNA that encodes for a specific protein is called a gene.
Like any molecule, DNA can participate in chemical reactions that change its structure. These changes are damaging because they interfere with the DNA’s normal function.
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For example, both environmental and cellular factors can cause double-strand breaks, in which the backbones of both DNA strands are severed, resulting in two completely separate pieces of DNA. Additionally, exposure to large amounts of energy, such as that from UV light produced by the sun, can cause two neighboring nucleotide bases to chemically attach to each other. Other chemicals within the cell can also attach themselves to individual nucleotides or actually connect the two strands of DNA together. One set of these chemicals is reactive oxygen species (ROS), which have gained research attention due to their relationship to both aging and cancer. Cells produce these molecules as byproducts when they make new cellular building blocks, during a stress response, or due to exposure to environmental sources like UV light.
Pigmentation, Skin Cancer, and DNA Damage
In their new study in Nature, Mitra and colleagues shed light on the role of ROS in melanoma. Decades ago, scientists linked exposure to UV light with various forms of skin cancer. UV light causes the formation of both ROS and linkages between neighboring nucleotides. Interestingly, scientists observed that a specific population of people — red heads with fair skin — have a particularly high incidence of melanoma, potentially because their skin cells produce very little of a certain type of pigment (hence their fair skin) thought to prevent UV light from penetrating skin cells and triggering DNA damage [4][5]. The new study contradicts this simple explanation [3].
Using mice with a preexisting mutation that sensitizes them to developing melanoma, the research team found that red-haired mice were more susceptible to cancer than dark-haired mice, even when they were never exposed to UV light [3]. Dark-haired mice produce two different pigments in their skin cells — pheomelanin and eumelanin, but red-haired mice produce only the first type. Eliminating both pigments to generate albino mice actually resulted in similar rates of cancer as dark-haired mice, suggesting that it’s not just decreased pigment levels (and correspondingly decreased protection from UV) that increase the risk of cancer in red heads. Rather, the ratio of the two different pigments is an important factor in preventing melanoma [3]. Dark-haired mice and albino mice are similar in the sense that they have balanced amounts of each pigment — either high amounts of both (dark-haired) or none of either (albino).
Earlier studies suggested that high levels of pheomelanin, the sole pigment present in red heads, lead to increased DNA damage caused by ROS following UV exposure [6][7]. When researchers in this current study looked at the DNA in red-haired mice, they found higher levels of ROS-specific DNA damage independently of UV exposure, indicating that the balance of two pigments is important to prevent DNA damage from cellular sources in addition to environmental sources (e.g. UV damage) [3]. Similar melanin pigments control hair and skin coloration in humans. Although this study does not negate the role of UV exposure in the development of cancer, it expands on our current understanding of how skin pigments contribute to DNA damage and melanoma.
The Future of DNA Repair Research and Applications to the Beauty Industry
Scientists have a general sense of how cells repair their DNA under different circumstances, but a lot of details are still unclear. Repair of damage caused by attaching small molecules like ROS to DNA is straightforward once cells detect the damage. However, because of the large number of distinct molecules that can modify DNA, cells require a diverse army of detection machinery to identify and fix different types of DNA damage. Repair of other types of damage, like double-strand breaks, require the coordinated activity of even more proteins.
Given the amount of DNA damage that accumulates in our cells and the number of proteins involved in DNA repair, it is not surprising that the beauty industry has created products intended to repair your DNA or prevent DNA damage. How lotions like sunscreen prevent DNA damage is obvious—they actually block UV light, thereby preventing several types of DNA damage from occurring. Others claim to provide antioxidants, molecules that counteract ROS. But how could a lotion trigger DNA repair? One idea is to deliver DNA repair proteins directly to cells. The FDA does not evaluate these cosmetic products, so only time and future research will tell if they actually work or not. Nonetheless, Mitra and colleagues note that preventative strategies other than simply blocking UV exposure may become important contributors in melanoma risk reduction in years to come [3].
Tammy Slenn is a PhD student in the department of Molecular and Cellular Biology.
Links of Interest
Nature News article on Mitra study, with podcast interview with principle investigator: http://www.nature.com/news/redhead-pigment-boosts-skin-cancer-risk-1.11711
Introduction to DNA damage and repair from Nature Education: http://www.nature.com/scitable/topicpage/dna-damage-repair-mechanisms-for-maintaining-dna-344
Fall 2012 SITN seminar: “Broken Genes: The Role of DNA Repair in Preventing Cancer” http://www.youtube.com/watch?feature=player_embedded&v=iXYL6dPyWJg
References
[1] Lombard, D.B., et al. (2005) DNA Repair, Genome Stability, and Aging. Cell, 120, 497-512.
[2] Lodish H, et al. (2008). Molecular Biology of the Cell, p145. WH Freeman: New York, NY. 6th ed.
[3] Mitra, D., et al. (2012) An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature, 491, 449-453.
[4] Rhodes, A.R. et al. (1987) Risk factors for cutaneous melanoma. A practical method of recognizing predisposed individuals. J. Am. Med. Assoc., 258, 3146-3154.
[5] World Health Organization: Ultraviolet radiation and the INTERSUN Programme http://www.who.int/uv/faq/skincancer/en/index2.html
[6] Wenczl, E. et al. (1998) Pheomelanin photosensitizes UVA-induced DNA damage in cultured human melanocytes. J. Invest. Dermatol, 111, 678-682.
[7] Hill, H.Z. & Hill, G.J. (2000) UVA, pheomelanin and the carcinogenesis of melanoma. Pigment Cell Res., 13, 140-144.