DCLRE1C

Description

The DCLRE1C (DNA cross-link repair 1C) is a protein-coding gene located on chromosome 10.

The DCLRE1C gene, also known as the Artemis gene, encodes a nuclear protein involved in V(D)J recombination and DNA repair. Artemis has endonuclease activity on 5' and 3' overhangs and hairpins when complexed with PRKDC. Artemis plays a key role in V(D)J recombination, the process by which B cell antibody genes and T cell receptor genes are assembled from individual V (variable), D (diversity), and J (joining) segments. This process involves the RAG (recombination activating gene) nuclease cutting both DNA strands adjacent to a V segment and a D segment, leading to the formation of hairpin structures at the coding ends. Artemis nuclease, in complex with DNA-dependent protein kinase (DNA‑PK), binds to these DNA ends and makes a single cut near the tip of the hairpin. This allows for deletion and addition of nucleotides, contributing to the diversity of antibody and T-cell receptor genes. Individuals deficient in Artemis cannot open hairpin ends, blocking V(D)J recombination and resulting in severe combined immune deficiency (SCID).

The DCLRE1C gene encodes a nuclease protein involved in DNA non-homologous end joining (NHEJ), crucial for repairing double-strand breaks and facilitating V(D)J recombination. This protein is essential for the V(D)J recombination process, which assembles exons encoding antigen-binding domains of immunoglobulins and T-cell receptor proteins from individual V, D, and J gene segments. The lymphoid-specific RAG endonuclease complex initiates V(D)J recombination by generating site-specific DNA double-strand breaks (DSBs), resulting in hairpin sealed coding ends and phosphorylated blunt signal ends. These ends undergo independent repair through the NHEJ pathway, forming coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity when isolated and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when complexed with PRKDC. The latter activity is essential for resolving closed hairpins before the formation of the coding joint. Additionally, it plays a role in repairing complex DSBs caused by ionizing radiation, which require substantial end-processing before religation by NHEJ.

DCLRE1C is also known as A-SCID, DCLREC1C, RS-SCID, SCIDA, SNM1C.

Associated Diseases

• Omenn syndrome
• Severe combined immunodeficiency with sensitivity to ionizing radiation
• Severe combined immunodeficiency due to DCLRE1C deficiency