The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila

The GATOR complex regulates an essential response to meiotic double-stranded breaks in Drosophila
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GATOR复合体调节果蝇减数分裂双链断裂的基本反应

DOI:
10.7554/elife.42149
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发表时间:
2018-09
期刊:
影响因子:
7.7
通讯作者:
Lilly Mary A
Lilly Mary A
中科院分区:
生物学1区
文献类型:
--
作者:
Wei Youheng;Bettedi Lucia;Ting Chun-Yuan;Kim Kuikwon;Zhang Yingbiao;Cai Jiadong;Lilly Mary A

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TORC1抑制剂GATOR1/SEACIT控制酵母的减数分裂进入和早期减数分裂事件。然而,代谢途径如何影响后生动物的减数分裂进程仍然知之甚少。在这里,我们报道了TORC1调节因子GATOR1和GATOR2在果蝇卵子发生过程中介导了对减数分裂双链断裂(DSB)的反应。我们发现减数分裂DSB触发了一条依赖GATOR1的途径的激活,该途径下调了雌性生殖系中的TORC1活性。在GATOR1突变体中,高TORC1活性导致减数分裂双链断裂的延迟修复和P53的过度激活。相反,需要GATOR2组分MIO来减弱GATOR1的活性,以确保减数分裂DSB不会引发永久性的生长停滞。出人意料的是,我们发现GATOR1在减数分裂DSB存在的情况下抑制反转录转座子的表达,其作用与P53平行。我们的研究揭示了短吻鳄复合体、减数分裂双链断裂的修复和反转录转座子表达之间的联系
The TORC1 inhibitor GATOR1/SEACIT controls meiotic entry and early meiotic events in yeast. However, how metabolic pathways influence meiotic progression in metazoans remains poorly understood. Here we report that the TORC1 regulators GATOR1 and GATOR2 mediate a response to meiotic double-stranded breaks (DSBs) during Drosophila oogenesis. We find that meiotic DSBs trigger the activation of a GATOR1 dependent pathway that downregulates TORC1 activity in the female germline. In GATOR1 mutants, high TORC1 activity results in the delayed repair of meiotic DSBs and the hyperactivation of p53. Conversely, the GATOR2 component Mio is required to attenuate GATOR1 activity, to ensure that meiotic DSBs do not trigger a permanent growth arrest. Unexpectedly, we found that GATOR1 inhibits retrotransposon expression in the presence of meiotic DSBs in a pathway that functions in parallel to p53. Our studies have revealed a link between the GATOR complex, the repair of meiotic DSBs and retrotransposon expression
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