Alternative titles; symbols
HGNC Approved Gene Symbol: AEN
Cytogenetic location: 15q26.1 Genomic coordinates (GRCh38): 15:88,604,683-88,632,281 (from NCBI)
Radiation can produce cell death by necrosis or apoptosis. Apoptosis is characterized by nuclear DNA fragmentation, condensed chromatin, and a fragmented nucleus. To identify factors involved in irradiation (IR)-induced apoptosis, Lee et al. (2005) used suppressive subtractive hybridization to screen differentially induced genes following ionizing radiation. They identified a novel gene, which they called apoptosis-enhancing nuclease (AEN), encoding a deduced 325-amino acid polypeptide with significant homology to various exonucleases.
Using RT-PCR, Lee et al. (2005) confirmed that expression of AEN was induced by IR. Cellular transfection and nuclease assays showed that AEN efficiently cleaved single-stranded, blunt end double-stranded, 3-prime recessed, and branched DNA, and less efficiently cleaved nicked and 5-prime recessed DNA. Experiments with AEN deletion mutants demonstrated that the exonuclease domain of AEN is crucial for its nuclease activity. Immunolocalization and cell fractionation experiments showed that AEN colocalizes with AIF (AIFM1; 300169) and CAD (DFFB; 601883) in the nucleus of irradiated cells. Transfection experiments demonstrated that expression of AEN acts to increase apoptosis 2-fold in the absence of irradiation and that cooperation exists between IR and AEN in apoptotic DNA degradation. Lee et al. (2005) suggested that AEN may contribute to radiation response during ionizing radiation-induced apoptosis by cooperatively cleaving DNA substrates along with other apoptotic nucleases and enhance apoptosis.
The International Radiation Hybrid Mapping Consortium mapped the ISG20L1 gene to chromosome 15 (RH44907).
Gross (2015) mapped the AEN gene to chromosome 15q26.1 based on an alignment of the AEN sequence (GenBank AF327352) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 2/17/2015.
Lee, J.-H., Koh, Y. A., Cho, C.-K., Lee, S.-J., Lee, Y.-S., Bae, S. Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis. Biochem. Biophys. Res. Commun. 337: 39-47, 2005. [PubMed: 16171785] [Full Text: https://doi.org/10.1016/j.bbrc.2005.08.264]