The article discusses the role of the Artemis gene in protecting children and mice from cancer. Initially identified as a factor involved in V(D)J recombination, mutations in the Artemis gene have been linked to immunodeficiency and a predisposition to lymphoma. Moshous et al. studied four patients with severe combined immunodeficiency (RS-SCID) and found that their peripheral blood lymphocytes had chromosome instabilities, particularly in regions containing Ig and T-cell receptor genes. The study also revealed a deficiency in N nucleotide additions at V(D)J junctions, suggesting that Artemis is involved in the NHEJ DNA-repair machinery. This is the first solid evidence that NHEJ mutations can be lymphomagenic in humans. Additionally, the article touches on the study by Fleming et al., which uses an evolutionary approach to identify missense mutations in the BRCA1 gene that are likely to be associated with cancer risk. The authors aligned GenBank sequences to identify conserved regions and found that missense mutations affecting fixed sites or resulting in non-conservative substitutions are more likely to be disease-causing. This method could be applied to other heritable diseases, such as β-globin pathologies. Finally, the article discusses a study by Lynda Chin and colleagues, which found that components of the retinoblastoma (RB) pathway are critical targets of UV mutagenesis in a murine melanoma model. UV exposure in mice with a history of sunburn led to earlier and more frequent melanoma development, primarily through the inactivation of the RB pathway. This suggests that analyzing RB pathway components in people with a history of sunburn could help in early detection of melanoma.The article discusses the role of the Artemis gene in protecting children and mice from cancer. Initially identified as a factor involved in V(D)J recombination, mutations in the Artemis gene have been linked to immunodeficiency and a predisposition to lymphoma. Moshous et al. studied four patients with severe combined immunodeficiency (RS-SCID) and found that their peripheral blood lymphocytes had chromosome instabilities, particularly in regions containing Ig and T-cell receptor genes. The study also revealed a deficiency in N nucleotide additions at V(D)J junctions, suggesting that Artemis is involved in the NHEJ DNA-repair machinery. This is the first solid evidence that NHEJ mutations can be lymphomagenic in humans. Additionally, the article touches on the study by Fleming et al., which uses an evolutionary approach to identify missense mutations in the BRCA1 gene that are likely to be associated with cancer risk. The authors aligned GenBank sequences to identify conserved regions and found that missense mutations affecting fixed sites or resulting in non-conservative substitutions are more likely to be disease-causing. This method could be applied to other heritable diseases, such as β-globin pathologies. Finally, the article discusses a study by Lynda Chin and colleagues, which found that components of the retinoblastoma (RB) pathway are critical targets of UV mutagenesis in a murine melanoma model. UV exposure in mice with a history of sunburn led to earlier and more frequent melanoma development, primarily through the inactivation of the RB pathway. This suggests that analyzing RB pathway components in people with a history of sunburn could help in early detection of melanoma.