Giving mice an enzyme lacking in most mammals allows them to better resist sunburn and skin cancer, and could do the same in humans. Researchers have engineered mice to be highly resistant to sunburn using enzymes that could protect against sunlight-induced skin cancer in humans. The enzymes, lacking in most mammals, repair DNA damage that can result from exposure to ultraviolet (UV) light. Insufficient repair, which can occur after unprotected sunbathing, can lead to cellular death—visible as sunburn—and permanent DNA mutations that result in skin cancer. Humans and many other mammals can remove DNA damage using a mechanism called nucleotide excision repair. This is an indirect process, however, as humans and most mammals lack a class of enzymes called photolyases that allow more direct repair. The enzymes target two major types of UV-induced DNA lesions, called cyclobutane pyrimidine dimers (CPDs) and (6-4)photoproducts (6-4PPs). Bert van der Horst and colleagues at Erasmus University Medical Center in Rotterdam wanted to determine the relative contribution of each type of lesion to cell death and cancer formation. So they gave mice transgenes for CPD and 6-4PP photolyase enzymes. They found that mice with the CPD photolyase transgene had greater resistance to UV irradiation than mice with the 6-4PP photolyase transgene. The mice could withstand higher doses of UV light than normal mice without developing sunburn, and also had higher resistance to UV-induced skin cancer. The research suggests that CPD lesions are more important for UV-induced cellular damage that leads to particular types of skin cancer. It also suggests that photolyases could be used as a genetic tool to fight UV-induced skin cancer in humans. The research is reported in the journal Current Biology.