Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control.
Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control.
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DOI：
10.7554/elife.61389
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发表时间：
2022-01-13
期刊：
影响因子：
7.7
通讯作者：
Calvi BR
中科院分区：
文献类型：
--
作者：
Chakravarti A;Thirimanne HN;Brown S;Calvi BR
人类和其它生物体中的p53基因家族成员编码大量蛋白质同种型，其功能在很大程度上是不确定的。以果蝇为模型，我们发现p53 B亚型主要在生殖细胞系中表达，与p53 A共定位于亚核小体。然而，只有p53 A介导生殖系和索马细胞对电离辐射的凋亡反应。相反，p53 A和p53 B都是减数分裂DNA断裂的正常修复所必需的，当减数分裂重组有缺陷时，这种活性更重要。我们发现，在卵母细胞与持久的DNA断裂p53 A也需要激活减数分裂粗线期检查点。我们的研究结果表明，果蝇p53异构体具有DNA损伤和细胞类型特异性功能，与哺乳动物p53家族成员在遗传毒性应激反应和卵母细胞质量控制中的功能相似。
p53 gene family members in humans and other organisms encode a large number of protein isoforms whose functions are largely undefined. Using Drosophila as a model, we find that a p53B isoform is expressed predominantly in the germline where it colocalizes with p53A into subnuclear bodies. It is only p53A, however, that mediates the apoptotic response to ionizing radiation in the germline and soma. In contrast, p53A and p53B are both required for the normal repair of meiotic DNA breaks, an activity that is more crucial when meiotic recombination is defective. We find that in oocytes with persistent DNA breaks p53A is also required to activate a meiotic pachytene checkpoint. Our findings indicate that Drosophila p53 isoforms have DNA lesion and cell type-specific functions, with parallels to the functions of mammalian p53 family members in the genotoxic stress response and oocyte quality control.