title: Defying DNA double-strand break-induced death during prophase I meiosis by temporal TAp63α phosphorylation regulation in developing mouse oocytes.
abstract: The dichotomy in DNA damage sensitivity of developing mouse oocytes during female germ line development is striking. Embryonic oocytes withstand hundreds of programmed DNA double-strand breaks (DSBs) required for meiotic recombination. Postnatal immature oocytes fail to tolerate even a few DSBs induced by gamma radiation treatment. TAp63α, a p53 family member, undergoes phosphorylation and mediates postnatal immature oocyte death following gamma radiation treatment, which is thought important for germ line quality maintenance. Whether prenatal meiotic oocytes tolerate DNA DSBs simply because they lack TAp63α expression is not clear. We found a significant number of oocytes in newborn mice initiate TAp63α expression and simultaneously carry meiotic DNA DSBs. However, the risk of premature death appears unlikely, because newborn oocytes strongly abate TAp63α phosphorylation induction and resist normally lethal doses of ionizing radiation damage. A calyculin A-sensitive Ser/Thr phosphatase activity downregulates TAp63α phosphorylation and ATM kinase mediates phosphorylation. Possible alterations in the relative balance of these counteracting activities during development may first temper TAp63α phosphorylation and death induction during meiotic DNA DSB repair and recombination, and afterward, implement germ line quality control in later stages. Insights into inherent DNA DSB resistance mechanisms in newborn oocytes may help prevent infertility in women in need of radiation or chemotherapy.
authors: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul, South Korea.
authors: Dal-Ah
authors: DA
authors: Kim
authors: Eun-Kyung
authors: EK
authors: Suh
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D005260:Female; D049469:Meiotic Prophase I / Q000235:genetics*; D051379:Mice; D009865:Oocytes / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics*; D010766:Phosphorylation / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D010750:Phosphoproteins; D015534:Trans-Activators; C486419:Trp63 protein, mouse; D004247:DNA