DCLRE1A

DCLRE1A, also known as SNM1A, is a human gene that encodes a protein involved in DNA repair, specifically in the homologous recombination pathway and the repair of DNA interstrand crosslinks (ICLs). The DCLRE1A protein is a component of the Fanconi anemia core complex, a multi-protein complex that is crucial for the activation of the Fanconi anemia pathway in response to DNA damage.

The DCLRE1A gene is located on chromosome 8q22.3. Mutations in DCLRE1A have been linked to a subtype of Fanconi anemia, specifically complementation group O (FA-O). Fanconi anemia is a rare genetic disorder characterized by bone marrow failure, developmental abnormalities, and an increased risk of cancer. Individuals with mutations in DCLRE1A exhibit hypersensitivity to DNA crosslinking agents, such as mitomycin C.

The DCLRE1A protein possesses exonuclease activity, which is important for its role in DNA repair. It works in concert with other proteins in the Fanconi anemia pathway to recognize, process, and repair damaged DNA, ensuring genomic stability. The protein's function is critical for cell survival, particularly in cells exposed to genotoxic stress. Research indicates it functions in conjunction with MUS81 to resolve stalled replication forks.

Deficiency in DCLRE1A can lead to defective DNA repair and an accumulation of DNA damage, ultimately contributing to the development of the clinical features associated with Fanconi anemia. Diagnosis of FA-O often involves genetic testing to identify mutations in the DCLRE1A gene.