Artemis is the Greek goddess that guards young children and small animals. The gene Artemis is therefore appropriately named, as it seems to be a genome guardian that protects children and mice from cancer. In the February issue of the Journal of Clinical Investigation, Moshous et al. associate mutations in Artemis with immunodeficiency and predisposition to lymphoma.

Artemis was initially identified as a factor involved in the non-homologous end-joining (NHEJ) phase of V(D)J recombination of T- and B-cell receptor genes. Disruption of this gene in mice resulted in a complete absence of T and B lymphocytes, as well as radiosensitivity.

Moshous et al. studied the effects of null and hypomorphic Artemis mutations in four patients from two families. These patients were born with radiosensitive severe combined immunodeficiency (RS-SCID), which is characterized by an absence of both mature B and T lymphocytes and gamma-ray sensitivity. After the appearance of lymphocytopaenia during infancy, the children developed severe infections, and two of the four developed B-cell lymphomas. Their peripheral blood lymphocytes were found to have chromosome instabilities — particularly in chromosomes where Ig and T-cell receptor genes were located. So, do these lymphocytes have defects in NHEJ DNA-repair machinery?

Moshous et al. found that T cells from these patients had a virtual absence of N nucleotide additions at the V(D)J junctions. N regions are non-templated nucleotides that are added to the 3′ ends of RAG-mediated double-strand breaks by the enzyme terminal deoxynucleotidyl transferase (TdT). N-region addition is known to require the NHEJ protein KU80, and these findings indicate that Artemis is also involved. Moshous et al. were able to complement the recombination deficiencies by re-expressing Artemis in the patient's fibroblasts, indicating that this gene alone is responsible for the DNA-repair defects.

This is some of the first solid evidence that NHEJ mutations are lymphomagenic in humans. Only one NHEJ deficiency has been found in humans — a hypomorphic mutation in ligase IV, which is associated with leukaemia and radiosensitivity — so the Artemis study is the first report of a human cancer that is associated with V(D)J defects. The authors suggest that other ill-defined immundeficiency conditions associated with lymphoma should be investigated for defects in NHEJ factors.