title: High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.
abstract: Ionizing radiation (IR) treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs) generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Shim
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea.
authors.forename: Eun-Mi
authors.initials: EM
authors.lastname: Lee
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea.
authors.forename: Long Duy
authors.initials: LD
authors.lastname: Nguyen
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul, Korea.
authors.forename: Jaekyung
authors.initials: J
authors.lastname: Shim
authors.affiliation: Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Korea.
authors.forename: Young-Han
authors.initials: YH
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D019521:Body Patterning / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D000071877:Checkpoint Kinase 1; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000528:radiation effects*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000528:radiation effects*; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects*; D015870:Gene Expression; D008540:Meiosis / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects; D009866:Oogenesis / Q000235:genetics / Q000528:radiation effects; D011839:Radiation, Ionizing; D059807:S Phase Cell Cycle Checkpoints / Q000528:radiation effects*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D000071877:Checkpoint Kinase 1; C000605877:grp protein, Drosophila