DNA cross-link repair 1C protein (DCLRE1C)

DNA cross-link repair 1C protein, commonly known as Artemis, is a critical nuclear enzyme involved in the non-homologous end joining (NHEJ) pathway of DNA double-strand break repair. It possesses 5'-to-3' exonuclease activity and, when complexed with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), acquires endonuclease activity capable of opening DNA hairpins generated during V(D)J recombination. This function is essential for the development of functional T and B lymphocytes, as it allows for the diversification of antigen receptors. Mutations in the DCLRE1C gene lead to Athabascan-type severe combined immunodeficiency (SCID) and Omenn syndrome, characterized by a lack of mature lymphocytes and extreme sensitivity to ionizing radiation. In oncology, Artemis is viewed as a therapeutic target because its inhibition can sensitize tumor cells to DNA-damaging agents like radiotherapy and certain chemotherapies. Conversely, gene therapy approaches are currently being utilized in clinical trials to restore Artemis function in pediatric patients with SCID.

Other names

ArtemisSNM1CA-V(D)J recombination-associated nucleaseSCIDRS-SCIDDNA repair protein Artemis

Gene replacement therapy for SCID; Inhibition of nuclease activity to sensitize cancer cells to radiotherapy and chemotherapy.