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A breakthrough article - published in the journal Nucleic Acids Research (NAR) - provides a better understanding of the process by which sunlight-induced DNA damage is recognized by the molecular repair machinery in cells as needing repair. Ultraviolet light from the sun is a ubiquitous carcinogen that can inflict structural damage to the cellular DNA. As DNA carries important blueprints for cellular functions, failure in removing and restoring damaged parts of DNA in a timely fashion can have detrimental outcomes and lead to skin cancers in humans.
The researchers showed how the repair protein Rad4/XPC would bind to one such UV-induced DNA damage - 6-4 photoproduct - to mark the damaged site along the DNA in preparation for the rest of the nucleotide excision repair (NER) process in cells. "The hallmark of NER is that it repairs a very broad range of DNA damage,” says lead author Jung-Hyun Min, Ph.D., associate professor of chemistry and biochemistry in Baylor's College of Arts & Sciences. “That is quite important in terms of how our genomes are protected from environmentally-caused DNA damage. While it has been known for many decades that this Rad4/XPC protein can recognize 6-4PP very efficiently, there has been no structure to show how it really binds to the lesion and why the recognition is so efficient compared with lesions such as CPD. Basically, our study nicely fills this missing gap and details what that mechanism must be." The study is called "Structure and mechanism of pyrimidine-pyrimidone (6-4) photoproduct recognition by the Rad4/XPC nucleotide excision repair complex."
"The hallmark of NER is that it repairs a very broad range of DNA damage,” Min added. “That is quite important in terms of how our genomes are protected from environmentally-caused DNA damage. While it has been known for many decades that this Rad4/XPC protein can recognize 6-4PP very efficiently, there has been no structure to show how it really binds to the lesion and why the recognition is so efficient compared with lesions such as CPD. Basically, our study nicely fills this missing gap and details what that mechanism must be."
Link Between Frequent Sun Exposure And Gene Fusion Found In Skin Cancer
Researchers from Kumamoto University, Japan have determined that a particular fusion gene has a tendency to be found in cutaneous squamous cell carcinoma (cSCC) lesions on skin exposed frequently to the sun. A fusion gene is a single composite gene that is the result of the combination of two formerly independent genes. Many cSCCs are easily treated by simple removal, but if left untreated they can become deadly. Current detection methods can be slow, particularly for abnormal cases, and some cSCCs are resistant to standard treatments emphasizing the need for improved diagnostics and therapies. Fusion genes may be found in various types of connective tissue tumors, and some treatments have been developed that inhibit the tumor-forming actions of those genes. However, no fusion gene had been identified for cSCC before the Kumamoto University research team began their search.
"We still have more work to do to determine this fusion gene's role in cSCC tumorigenesis, but our work should provide some insights into new drug development for this type of cancer," says project scientist Dr. Sho Egashira. "It may be possible, for example, to assess the fusion genes in a cancerous lesion and apply a customized therapy based on the results. This would greatly reduce the risk of any side effects of the treatment."
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With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.
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Founder Ray Spotts has a passion for all things natural and has made a life study of nature as it relates to health and well-being. Ray became a forerunner bringing products to market that are extraordinarily effective and free from potentially harmful chemicals and additives. For this reason Ray formed Trusted Health Products, a company you can trust for clean, effective, and healthy products. Ray is an organic gardener, likes fishing, hiking, and teaching and mentoring people to start new businesses. You can get his book for free, “How To Succeed In Business Based On God’s Word,” at www.rayspotts.com.
