Alternative titles; symbolsSNM1, S. CEREVISIAE, HOMOLOG OF; SNM1SNM1, S. CEREVISIAE, HOMOLOG OF, A; SNM1AKIAA0086HGNC Approved Gene Symbol: DCLRE1ACytogenetic lo...
Alternative titles; symbols
HGNC Approved Gene Symbol: DCLRE1A
Cytogenetic location: 10q25.3 Genomic coordinates (GRCh38): 10:113,834,724-113,854,393 (from NCBI)
DNA interstrand cross-links prevent strand separation, thereby physically blocking transcription, replication, and segregation of DNA. DCLRE1A is one of several evolutionarily conserved genes involved in repair of interstrand cross-links (Dronkert et al., 2000).
▼ Cloning and Expression
By sequencing clones obtained from a size-fractionated human immature myeloid cell line cDNA library, Nagase et al. (1995) cloned DCLRE1A, which they called KIAA0086. The deduced 1,040-amino acid protein shares 33.3% identity over 192 amino acids with the S. cerevisiae DNA repair protein Snm1. Northern blot analysis detected expression in all tissues and cell lines examined except peripheral blood leukocytes.
Dronkert et al. (2000) determined that human DCLRE1A, which they called SNM1, contains a nuclear localization signal and a zinc finger motif in its N-terminal half and 8 motifs shared with SNM1-like proteins of various species in its C-terminal half. Fluorescence-tagged SNM1 localized to nuclei of transfected human fibroblasts and Chinese hamster ovary cells, but it was excluded from nucleoli.
Using Northern blot analysis, Richie et al. (2002) detected a 4.5-kb SNM1 transcript in all tissues examined, with highest expression in pancreas and brain. Fluorescence-tagged SNM1 localized to the nucleus of individual transfected HeLa and human breast carcinoma cells in 3 distinct patterns: diffuse nuclear staining, multiple nuclear foci, or 1 or 2 larger nuclear bodies.
▼ Gene Function
Dronkert et al. (2000) found that cells overexpressing human SNM1 underwent morphologic changes consistent with apoptosis a few days after SNM1 introduction.
Richie et al. (2002) found that exposure of cells to ionizing radiation or to an interstrand cross-linking agent altered the pattern of SNM1 nuclear localization. Under these conditions, the number of cells exhibiting SNM1 bodies decreased and the population of cells with SNM1 foci increased. Immunofluorescence studies indicated that SNM1 colocalized with 53BP1 (TP53BP1; 605230) before and after exposure to ionizing radiation, and coimmunoprecipitation assays confirmed the interaction. SNM1 foci formed after ionizing radiation were largely coincident with foci formed by MRE11 (MRE11A; 600814) and to a lesser extent with those formed by BRCA1 (113705), but not with those formed by RAD51 (179617). Focus formation by SNM1 did not require ATM (607585).
▼ Gene Structure
Demuth and Digweed (1998) determined that the DCLRE1A gene contains 9 exons and spans about 20 kb. The upstream region contains a GC box, but no TATA box, and has 1 SP1 (189906) site, 3 AP1 (see JUN; 165160) sites, 4 AP4 (TFAP4; 600743) sites, and 1 NFKB (see 164011) site.
By examining a panel of human-rodent hybrid cell lines, Nagase et al. (1995) mapped the DCLRE1A gene to chromosome 10.
▼ Animal Model
Dronkert et al. (2000) found that Snm1 -/- mice were viable and fertile and showed no major abnormalities, but they were hypersensitive to mitomycin C compared with wildtype mice. Snm1 -/- mouse embryonic stem cells grew at a rate comparable to wildtype stem cells, but they were 2-fold more sensitive to mitomycin C. Mutant and wildtype stem cells showed the same sensitivity to other DNA interstrand cross-linking agents, ultraviolet irradiation, and gamma irradiation.