Sunlight damages human DNA tens to hundreds of thousands of times per cell per day, and scientists have just discovered a second, previously unknown way that cells repair that damage. For decades, researchers believed that human cells had only one tool—nucleotide excision repair (NER)—to fix the specific kind of DNA damage caused by ultraviolet light. When NER fails, people develop xeroderma pigmentosum, a condition that makes them extremely prone to skin cancer. The newly identified pathway, called BER-dependent photodimer repair, works independently of NER and may explain why some people are more or less vulnerable to sunlight-induced mutations. This is fundamental science. The immediate goal is to understand how this second repair system operates, which genes control it, and whether it can be boosted. If the team succeeds in mapping the pathway, the long-term possibility is a therapeutic strategy to reduce skin cancer risk in people with defective NER or in the general population. Past discoveries of DNA repair pathways have already led to cancer prevention strategies and treatments; this one could add a new layer of protection against the most common human carcinogen—sunlight.
View original technical description
The stability and integrity of DNA, our genetic material, is constantly threatened by endogenous and exogenous sources of DNA damage. As a consequence, multiple biochemical pathways exist in human cells that detect and repair DNA damage, thereby reducing genetic mutation and the risk of developing cancer and/or a range of other diseases, including neurodevelopmental dysfunction and neurodegeneration. Breaks in one strand of the DNA double helix are denoted DNA single-strand breaks (SSBs) and are the most common DNA lesions arising in cells, at a frequency of tens-to-hundreds of thousands per cell per day. If not repaired rapidly, SSBs can disrupt DNA replication, transcription, and can result in neurological disease. Recently, we identified and reported a new role for the biochemical pathway that repairs SSBs (single-strand break repair; SSBR) in the repair of sunlight-induced DNA photodimers1. It has long been believed that that the only available pathway for the repair of photodimers in normal human cells is a DNA repair pathway known as nucleotide excision repair (NER); a complex process that is defective in the highly cancer-prone human disease, xeroderma pigmentosum (XP). However, our discovery of an NER-independent pathway for the repair of sunlight-induced photodimers overturns this concept, and we have named this new pathway base excision repair-dependent photodimer repair (BER-dependent PDR)1. Our discovery opens up important questions concerning how human cells protect their genome from sunlight-induced DNA damage and mutation. We will address these questions by conducting the experiments outlined in the current application, and we will address the possibility that we can exploit our understanding of this new pathway for therapeutic purposes, to reduce the risk in people of sunlight-induced genetic mutations and skin cancer.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know