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p63 protects the female germ line during meiotic arrest

机译：p63在减数分裂阻滞过程中保护雌性生殖系

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摘要

Meiosis in the female germ line of mammals is distinguished by a prolonged arrest in prophase of meiosis I between homologous chromosome recombination and ovulation(1). How DNA damage is detected in these arrested oocytes is poorly understood, but it is variably thought to involve p53, a central tumour suppressor in mammals(2-4). While the function of p53 in monitoring the genome of somatic cells is clear, a consensus for the importance of p53 for germ line integrity has yet to emerge. Here we show that the p53 homologue p63 (refs 5, 6), and specifically the TAp63 isoform, is constitutively expressed in female germ cells during meiotic arrest and is essential in a process of DNA damage-induced oocyte death not involving p53. We also show that DNA damage induces both the phosphorylation of p63 and its binding to p53 cognate DNA sites and that these events are linked to oocyte death. Our data support a model whereby p63 is the primordial member of the p53 family and acts in a conserved process of monitoring the integrity of the female germ line, whereas the functions of p53 are restricted to vertebrate somatic cells for tumour suppression. These findings have implications for understanding female germ line fidelity, the regulation of fertility and the evolution of tumour suppressor mechanisms.
机译：哺乳动物雌性生殖系中的减数分裂的特征是同源染色体重组和排卵之间减数分裂I的前期时间延长（1）。人们对如何在这些停滞的卵母细胞中检测到DNA损伤的方法知之甚少，但据不同地认为，它涉及哺乳动物中的中央肿瘤抑制因子p53（2-4）。尽管p53在监测体细胞基因组中的功能很明确，但对于p53对种系完整性的重要性尚未达成共识。在这里，我们显示p53同源物p63（参考文献5、6），特别是TAp63亚型在减数分裂停滞期间在女性生殖细胞中组成性表达，并且在不涉及p53的DNA损伤诱导的卵母细胞死亡过程中至关重要。我们还表明，DNA损伤诱导p63磷酸化及其与p53同源DNA位点的结合，并且这些事件与卵母细胞死亡有关。我们的数据支持一个模型，其中p63是p53家族的主要成员，并在保守的过程中起作用以监测雌性种系的完整性，而p53的功能仅限于脊椎动物的体细胞以抑制肿瘤。这些发现对理解女性种系的保真度，生育力的调节和抑癌机制的演变具有重要意义。

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