Synopsis
Under the leadership of Associate Professor TANAKA Kiyoji of the Human Cell Biology Group, Graduate School of Frontier Biosciences, Osaka University, a team of researchers has discovered, for the first time in the world, a gene responsible for UV-stimulated scaffold protein A (UVSSA) characterized by skin reddening, numerous freckles and marked dark spots caused by repair-deficiency disorder of DNA damaged by UV.
This group has also clarified that a UVSSA gene product is essential for stabilizing other DNA repair proteins. This outstanding feat was published in online news at the website of Nature Genetics , the American science magazine, on April 1, 2012 at 6:00 p.m. GMT.
Background
Exposure to UV radiation damages the DNA in skin cells. (Figure 1) Cells have a function to repair DNA damage and prevent the death of cells and mutations caused by DNA damage as well as aging and canceration. However, Ultraviolet-Sensitive Syndrome (UVSS) patients have abnormalities in the repair mechanism for DNA damage. They lack the mechanism to selectively repair DNA damage that prevents the transcription process from making messenger RNA from DNA, genetic blueprints. Therefore, once DNA is damaged, the transcription cannot be resumed, inducing the death of cells. (Figure 2) For that reason, in UVSS patients, the skin exposed to sunlight becomes red, developing numerous freckles and marked dark spots. However, DNA damage that blocks the process of making messenger RNA, inducing the death of cells; therefore, DNA is damaged by UV, but that does not lead to skin cancer.
Findings
The cells of UVSS patients show UV hypersensitivity. This research group introduced mouse chromosomes into UVSS patient cells and acquired normal levels of UV resistance. Then the group clarified that the gene responsible for UVSSA was located in mouse chromosome 5. Furthermore, the group identified the position of the causative gene on the mouse chromosome 5 using a DNA microarray and also identified the human casual gene for UVSS by homologious gene in mice.
Additionally, the group clarified that UVSS patients have a mutation in this gene. The group analyzed the role of UVSSA gene in a DNA repair mechanism and found that it is necessary for stabilizing repair proteins in the mechanism of selectively repairing DNA damage that blocks the transcription process. (Figure 3) Thus, it was found that the UVSSA gene is also essential for resuming the transcription process after repairing DNA. (Figure 4)
Future development
The discovery of UVSSA gene will provide important information in clarifying the mechanism to selectively repair the DNA damage that blocks the transcription process in humans. Cockayne Syndrome is another inherited disease with a defect in the DNA repair mechanism. Cockayne Syndrome has disorders such as growth failure, neural symptom, and premature aging in addition to photosensitivity. The reason why the clinical symptoms of ultraviolet-sensitive syndrome and Cockayne Syndrome are significantly different, although they share a defect in the same gene and DNA repair mechanism has been unknown.
The discovery of UVSSA gene will lead to finding solutions for this question. Some healthy people have photosensitivity and numerous freckles and marked dark spots. It is necessary to consider the possibility that those people might have a mutation in the UVSSA gene. The discovery of UVSSA gene will lead to the prevention of freckles associated with aging. One possibility is to instruct persons diagnosed with ultraviolet-sensitive syndrome by gene analysis to avoid exposure to the sun as much as possible.

Figure 4