Image: Most UVRAG complexes, multifunctional. UVRAG directly binds phosphorylated Bif, Beclin 1, Bax, CEP63 and DNA-PK, forming distinct protein complexes to regulate autophagosome formation, autophagosome maturation, endosome maturation, apoptosis, centrosome stability, DNA repair and genomic stability.
A new USC-led study identified a “sunscreen” gene that may help stave off skin cancer. The researchers found “UV radiation Resistance Associated Gene”, UVRAG, is a tumor suppressor for skin cancer, the most common form of cancer in the US. Melanoma is the deadliest skin cancer. In fact, melanoma rates have doubled over the last 3 decades. “If we understand how this UV-resistant gene functions and the processes by which cells repair themselves after ultraviolet damage, then we could find targets for drugs to revert a misguided mechanism back to normal conditions,” said A/Prof Chengyu Liang, USC.
More than 90% of melanoma skin cancers develop because of cell damage from exposure to UV radiation. Melanoma kills about 10,130 people annually. “People who have the mutated UV-resistant gene or low levels of the UV-resistant gene may be at higher risk of melanoma or other skin cancers, especially if they go sunbathing or tanning frequently,” Liang said. “Our study suggests that the UV-resistant gene may serve as a biomarker for skin cancer prevention.”
Method: They used data from 340 melanoma patients who participated in The Cancer Genome Atlas. The study also included 2 experimental groups with either reduced levels of the UV-resistant gene or a mutant copy of that gene in melanoma cells and 50 fly eyes. The control groups were melanoma cells or fly eyes with normal copies of the UV-resistant gene. The scientists gave a UV shot to cells carrying the normal UV-resistant gene and cells carrying defective copies of it. After 24 hours, cells carrying normal versions of the gene had repaired more than 50% of the UV-induced damage. In contrast, the defective samples repaired <20% of the damaged cells.
“That means when people sunbathe or go tanning, those who have the normal UV-resistant gene can repair most UV-induced DNA burns in a timely manner, whereas those with the defective UV-resistant gene will have more damage left unrepaired,” Liang said. “After daily accumulation, if they sunbathe or go tanning often, these people will have increased risk for developing skin cancers such as melanoma.”
The researchers were able to show a correlation with increased cancer risk. Their study did not definitively say diminished levels or mutant copies of the UV-resistant gene were causes for skin cancer development.
Scientists first discovered the UV-resistant gene nearly 2 decades ago in relation to Xeroderma Pigmentosum, which makes people extremely sensitive to sunlight and puts them at high risk for developing skin cancer. Scientists did not examine the function of the UV-resistant gene in people who are healthy or who have skin cancer.
“The UV-resistant gene is a tumor suppressor involved in the UV-repair process of a cell’s DNA and is essential for preventing UV-induced genomic instability,” Yang said. “When the UV-resistant gene is lost, the cell cannot efficiently repair UV- and chemical-induced damage.”
The UV-resistant gene is involved in the multistep DNA cell-repair process. First a known protein scans for damaged DNA. Once it finds lesions, it tags the UV-resistant gene into action. The UV-resistant gene is like a humanitarian convoy dropping off reinforcements or aid to help damaged areas repair at precisely the right time. The researchers did not have data from people without skin cancer, so they were unable to compare their observations of melanoma patients with those of skin cancer-free people.
“We found the expression level of the UV-resistant gene is related to melanoma patients’ survival and metastasis stages,” Yang said. “Lower levels of the UV-resistant gene means a lower survival rate and advanced metastases stages.” UV exposure, frequent trips to the tanning salon and genetics all play a role in developing skin cancer. Studies have shown, for example, that redheads are more prone to skin cancer because of their genetic background. Liang, Yang et al have identified a new player in the skin cancer field.
“To our knowledge, the UV-resistant gene does not have any enzymic activity; It’s a supporter or coordinator,” Liang said. “Although it may not be the direct doer, without it, the whole structure collapses.” Future studies will use mouse models to better understand how the UV-resistant gene functions. Yang said. “Perhaps one day a drug could stimulate the repairing functionality of the UV-resistant gene to ensure swift and effective repair of UV-damaged skin cells. That would be a good treatment for people who are at high risk of developing skin cancer.” http://news.usc.edu/100824/sunscreen-gene-may-help-protect-against-skin-cancer/
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