Disease relevance of DCLRE1A

• The homology of the KIAA0086 gene to the yeast SNM1 gene, which is involved in the cellular response to DNA-interstrand crosslinks, is discussed with respect to a possible role of the KIAA0086 gene in the human disorder, Fanconi anemia [1].
• Two of the remaining 3 patients had no alterations of PSO2 or PSCO2 associated with airway obstruction during sleep [2].

High impact information on DCLRE1A

• Here we demonstrate that the proteins Snm1, -2, and -4 are required for the secretion of ESAT-6 and CFP-10, small proteins previously identified as major T cell antigens [3].
• These findings suggest that Snm1 is a component of a mitotic stress checkpoint that negatively targets the APC prior to chromosome condensation [4].
• Specifically, we found that compared to wild-type cells, Snm1-deficient mouse embryonic fibroblasts exposed to spindle poisons exhibited elevated levels of micronucleus formation, decreased mitotic delay, a failure to arrest in mitosis prior to chromosome condensation, supernumerary centrosomes, and decreased viability [4].
• DNA cross-link repair protein SNM1A interacts with PIAS1 in nuclear focus formation [5].
• The yeast SNM1/PSO2 gene specifically functions in DNA interstrand cross-link (ICL) repair, and its role has been suggested to be separate from other DNA repair pathways [5].

Biological context of DCLRE1A

• To explore the functional role of human Snm1 in response to DNA damage, we characterized the cellular distribution and dynamics of human Snm1 before and after exposure to DNA-damaging agents [6].
• Analysis of the upstream untranscribed region identified one GC box but no TATA box, suggesting that the KIAA0086 gene is a housekeeping gene [1].
• The hSNM1 contains a long 5' untranslated region (5'UTR) predicted to fold into a complex secondary structure, and which contains numerous short open reading frames (ORFs) [7].
• One patient had a large genomic deletion, but the other 3 patients carried simple missense mutations in conserved amino acid residues in the SNM1 homology domain of the Artemis protein [8].
• The cells containing the missense mutations in the SNM1 homology domain had the same recombination phenotype as the cells with the large deletion, indicating that these amino acid residues are indispensable for Artemis function [8].

Anatomical context of DCLRE1A

• Human Snm1 was found to localize to the cell nucleus in three distinct patterns [6].
• We show here using bicistronic constructs that human SNM1 mRNA contains an internal ribosome entry site (IRES) that generally suppresses translation, except during mitosis where translation is upregulated [7].

Associations of DCLRE1A with chemical compounds

• The effect of externally applied load on the partial pressure of oxygen in tissue, measured at the skin surface (PSO2) was examined by applying a load to a transcutaneous O2 monitor mounted on the skin of healthy subjects [9].

Other interactions of DCLRE1A

• These results suggest that interaction between SNM1A and PIAS1 is required for ICL repair [5].

Analytical, diagnostic and therapeutic context of DCLRE1A

• Indirect immunofluorescence studies also indicated that the human Snm1 protein colocalized with 53BP1 before and after exposure to ionizing radiation, and a physical interaction was confirmed by coimmunoprecipitation assays [6].
• Skin oxygen tension, PSO2 was monitored continuously during and for 35 min after treatment [10].

References