Defying DNA Double-Strand Break-Induced Death during Prophase I Meiosis by Temporal TAp63α Phosphorylation Regulation in Developing Mouse Oocytes
Defying DNA Double-Strand Break-Induced Death during Prophase I Meiosis by Temporal TAp63α Phosphorylation Regulation in Developing Mouse Oocytes
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在发育中的小鼠卵母细胞中，通过对TAp63α磷酸化的时序调控，在减数分裂前期I阶段抵御DNA双链断裂诱导的死亡
DOI：
10.1128/mcb.01223-13
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发表时间：
2014-04-01
影响因子：
5.3
通讯作者：
Suh, Eun-Kyung
中科院分区：
文献类型：
--
作者：
Kim, Dal-Ah;Suh, Eun-Kyung
小鼠卵母细胞在雌性生殖系发育过程中DNA损伤敏感性的二分法是惊人的。胚胎卵母细胞承受减数分裂重组所需的数百个程序性DNA双链断裂（DSB）。出生后未成熟的卵母细胞不能耐受甚至一些由γ辐射处理诱导的DSB。TAp 63 α是p53家族成员，在γ射线处理后经历磷酸化并介导出生后未成熟卵母细胞死亡，这被认为对生殖系质量维持很重要。产前减数分裂卵母细胞是否仅仅因为缺乏TAp 63 α表达而耐受DNA DSB尚不清楚。我们发现新生小鼠中大量卵母细胞启动TAp 63 α表达，同时携带减数分裂DNA DSB。然而，过早死亡的风险似乎不太可能，因为新生卵母细胞强烈减弱TAp 63 α磷酸化诱导，并抵抗通常致死剂量的电离辐射损伤。Calyculin A敏感的Ser/Thr磷酸酶活性下调TAp 63 α磷酸化，ATM激酶介导磷酸化。在发育过程中这些抵消活动的相对平衡的可能改变可能首先在减数分裂DNA DSB修复和重组过程中回火TAp 63 α磷酸化和死亡诱导，然后在后期阶段实施生殖系质量控制。深入了解新生卵母细胞中固有的DNA DSB抗性机制可能有助于预防需要放疗或化疗的女性不孕症。
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. TAp63 alpha, 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 TAp63 alpha expression is not clear. We found a significant number of oocytes in newborn mice initiate TAp63 alpha expression and simultaneously carry meiotic DNA DSBs. However, the risk of premature death appears unlikely, because newborn oocytes strongly abate TAp63 alpha phosphorylation induction and resist normally lethal doses of ionizing radiation damage. A calyculin A-sensitive Ser/Thr phosphatase activity downregulates TAp63 alpha phosphorylation and ATM kinase mediates phosphorylation. Possible alterations in the relative balance of these counteracting activities during development may first temper TAp63 alpha 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.