DNA Damaged Induced Cell Death in Oocytes.
DNA Damaged Induced Cell Death in Oocytes.
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DOI：
10.3390/molecules25235714
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发表时间：
2020-12-03
期刊：
影响因子：
--
通讯作者：
Dötsch V
中科院分区：
文献类型：
--
作者：
Gebel J;Tuppi M;Sänger N;Schumacher B;Dötsch V
通过减数分裂产生单倍体配子是有性生殖原理的核心。通过交换机制，同源染色体之间的遗传物质交换进一步增强了遗传多样性。这一机制不仅需要同源染色体的正确配对，而且需要诱导的DNA双链断裂的有效修复。卵母细胞已经进化出一种独特的质量控制系统，如果染色体不正确排列或DNA修复不可能，则会消除细胞。从线虫和果蝇到人类的这种监测系统的核心是p53蛋白家族，并且在脊椎动物中特别是p63。在哺乳动物中，卵母细胞在减数分裂I的前期储存很长一段时间，在人类中，可以持续50多年。在整个逮捕阶段，DNA损伤检查点保持活跃。用DNA损伤性辐射或化疗药物治疗女性癌症患者激活了这个检查点，导致卵母细胞池的消除，从而导致过早绝经和不孕。在这里，我们回顾了这种质量控制系统的分子机制，并讨论了化疗期间卵母细胞池保存的潜在治疗干预。
The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.
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影响因子：
64.5
作者：
Deutsch GB;Zielonka EM;Coutandin D;Weber TA;Schäfer B;Hannewald J;Luh LM;Durst FG;Ibrahim M;Hoffmann J;Niesen FH;Sentürk A;Kunkel H;Brutschy B;Schleiff E;Knapp S;Acker-Palmer A;Grez M;McKeon F;Dötsch V
通讯作者：
Dötsch V
影响因子：
9
作者：
Bildik, Gamze;Acilan, Ceyda;Oktem, Ozgur
通讯作者：
Oktem, Ozgur
DOI：
10.1073/pnas.0900383106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Burge, Sarah;Teufel, Daniel P.;Fersht, Alan R.
通讯作者：
Fersht, Alan R.
影响因子：
3.3
作者：
Doll, Markus Alexander;Soltanmohammadi, Najmeh;Schumacher, Bjoern
通讯作者：
Schumacher, Bjoern
影响因子：
4
作者：
Browne, Gareth;Cipollone, Rita;Melino, Gerry
通讯作者：
Melino, Gerry