Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis

To investigate ionizing radiation response, we screened genes that exhibit higher expression following γ irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to t...

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Published inBiochemical and biophysical research communications Vol. 337; no. 1; pp. 39 - 47
Main Authors Lee, Ji-Hyun, Koh, Yeon A., Cho, Chul-Koo, Lee, Su-Jae, Lee, Yun-Sil, Bae, Sangwoo
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 11.11.2005
Subjects
Amino Acid Sequence
APOPTOSIS
Apoptosis enhancing nuclease
Apoptosis Inducing Factor
Base Sequence
Cell Line, Tumor
Cell Nucleus - enzymology
Deoxyribonucleases - analysis
DNA
DNase
Exodeoxyribonucleases - analysis
Exodeoxyribonucleases - genetics
Exodeoxyribonucleases - metabolism
Flavoproteins - analysis
GAMMA RADIATION
Gamma Rays
Gene Expression - radiation effects
GENES
Humans
Ionizing radiation
IRRADIATION
Membrane Proteins - analysis
Molecular Sequence Data
MUTANTS
NUCLEASES
Radiation response
RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
STRUCTURAL CHEMICAL ANALYSIS
SUBCELLULAR DISTRIBUTION
SUBSTRATES
Ionizing radiation
DNase
Radiation response
Apoptosis enhancing nuclease
Apoptosis
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Summary:To investigate ionizing radiation response, we screened genes that exhibit higher expression following γ irradiation. We report here the isolation and functional characterization of a novel ionizing radiation-induced gene, AEN. Sequence analysis of AEN revealed exonuclease domain highly similar to that of exonuclease III. The AEN protein revealed DNase activity by cleaving various DNA substrates. Subcellular distribution of AEN exhibited nuclear colocalization with apoptotic nucleases such as CAD and AIF following irradiation. Moreover AEN distribution revealed perinuclear staining pattern which could be seen with other apoptotic nucleases. Irradiation of AEN-expressing cells resulted in synergistic increase of apoptosis whereas AEN deletion mutant in exonuclease domain did not. Our data, thus, suggest that radiation-induced AEN cleaves DNA in concert with other apoptotic nucleases and thereby enhances apoptosis following ionizing irradiation.
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ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.08.264