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Enzyme, lost in most mammals, is shown to protect against UV-induced skin cancer

In a finding that broadens our insight into the cause of certain kinds of UV-induced skin cancer, researchers at Erasmus University Medical Center (Rotterdam, The Netherlands) have employed an evolutionarily ancient enzyme-repair system to identify the principal type of DNA damage responsible for the onset of skin-tumor development. The researchers' findings also suggest that this enzyme system may be useful in developing preventative therapies against skin cancer.

Ultraviolet light is a known source of damage to our DNA, but under normal conditions humans and other mammals are capable of removing UV-induced DNA damage by a DNA repair mechanism called nucleotide excision repair. Insufficient repair of UV-induced DNA damage, which for example may occur after excessive unprotected sunbathing, can lead to cellular death ?recognized as sunburn of the skin ?and may cause permanent changes in the DNA (mutations) that ultimately can result in the onset of skin cancer. Thus far it was not clear how the two major types of UV-induced DNA lesions ?cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs) ?contribute to the processes of cell death and cancer formation. Identifying the relative contributions of the two types of damage to tumor formation is critical for the development of therapies that could help prevent skin cancer. Moreover, CPDs and 6-4PPs have particular potential to cause lasting damage to mammalian cells because photolyases ?a class of enzymes capable of efficiently repairing these lesions ?have apparently been lost from placental mammals over the course of evolution. Thus, most mammals, including humans, can only repair these lesions through a much less direct and elaborate process called nucleotide excision repair. In the new work, Dr. Bert van der Horst and colleagues studied the effects of CPD and 6-4PP lesions by providing mice with transgenes encoding CPD and 6-4PP photolyase enzymes. Although mice do not ordinarily produce these en
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Source:Eurekalert


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