DNA cross-link repair 1C (DCLRE1C) (DCLRE1C)

DNA cross-link repair 1C (DCLRE1C), commonly known as Artemis, is a nuclear enzyme essential for the repair of DNA double-strand breaks via the non-homologous end joining (NHEJ) pathway (UniProt Q96SD1). It exhibits 5' to 3' exonuclease activity and, when activated by the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), acts as an endonuclease to process DNA hairpins during V(D)J recombination (PubMed: 11832225). This activity is indispensable for the maturation of T and B lymphocytes, making it a cornerstone of the adaptive immune system. Mutations in the DCLRE1C gene lead to Artemis-deficient severe combined immunodeficiency (RS-SCID), a condition marked by profound lymphopenia and cellular radiosensitivity (NIH: GARD). Current therapeutic interventions involve ex vivo gene therapy, where autologous CD34+ hematopoietic stem cells are transduced with a lentiviral vector carrying a functional DCLRE1C gene to restore immune competence in affected patients (NEJM: 10.1056/NEJMoa2206555).

Other names

ArtemisSNM1CSCIDNRS-SCIDDNA cross-link repair protein 1CA-SCID

Gene addition to restore functional Artemis protein expression in hematopoietic stem cells