Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of gurken through Chk2/Mnk
Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of gurken through Chk2/Mnk
复制标题
DOI：
10.1016/s0960-9822(02)01165-x
复制
发表时间：
2002-10-01
期刊：
影响因子：
9.2
通讯作者：
Schüpbach, T
中科院分区：
文献类型：
--
作者：
Abdu, U;Brodsky, M;Schüpbach, T
背景：在果蝇卵发生过程中，未修复的双链DNA断裂激活了一个依赖于mei-41的减数分裂检查点，该检查点将减数分裂的进展与特定的发育过程结合在一起。这个检查点影响Gurken蛋白（一种转化生长因子a样信号分子）的积累，以及卵母细胞核的形态。然而，该检查点在果蝇中的组成尚未完全阐明。结果：我们发现果蝇Chk2同源基因（DmChk2/Mnk）的突变抑制了gurken mRNA的翻译缺陷和卵母细胞核形态的缺陷。我们还发现DmChk2在mei-41依赖性途径中磷酸化。对减数分裂细胞周期进程的分析表明，果蝇的Chk2同源性在减数分裂早期不需要，而秀丽隐杆线虫的Chk2已被观察到。我们证明，减数分裂检查点的激活影响Dwee1的定位，并与Dwee1的dmchk2依赖性翻译后修饰有关。我们认为Dwee1在减数分裂检查点中发挥作用，调节减数分裂细胞周期，但不参与gurken mRNA的翻译。此外，我们发现p53和mus304，果蝇ATR-IP同源物，并不是由减数分裂DNA修复突变引起的图案缺陷所必需的。结论：DmChk2是苍蝇减数分裂检查点的一个换能器，它被未修复的双链DNA断裂激活。DmChk2在这个特定检查点的激活影响细胞周期调节因子以及mRNA翻译。
Background: During Drosophila oogenesis, unrepaired double-strand DNA breaks activate a mei-41-dependent meiotic checkpoint, which couples the progression through meiosis to specific developmental processes. This checkpoint affects the accumulation of Gurken protein, a transforming growth factor a-like signaling molecule, as well as the morphology of the oocyte nucleus. However, the components of this checkpoint in flies have not been completely elucidated.Results: We show that a mutation in the Drosophila Chk2 homolog (DmChk2/Mnk) suppresses the defects in the translation of gurken mRNA and also the defects in oocyte nuclear morphology. We also found that DmChk2 is phosphorylated in a mei-41-dependent pathway. Analysis of the meiotic cell cycle progression shows that the Drosophila Chk2 homolog is not required during early meiotic prophase, as has been observed for Chk2 in C. elegans. We demonstrate that the activation of the meiotic checkpoint affects Dwee1 localization and is associated with DmChk2-dependent posttranslational modification of Dwee1. We suggest that Dwee1 has a role in the meiotic checkpoint that regulates the meiotic cell cycle, but not the translation of gurken mRNA. In addition, we found that p53 and mus304, the Drosophila ATR-IP homolog, are not required for the patterning defects caused by the meiotic DNA repair mutations.Conclusions: DmChk2 is a transducer of the meiotic checkpoint in flies that is activated by unrepaired double-strand DNA breaks. Activation of DmChk2 in this specific checkpoint affects a cell cycle regulator as well as mRNA translation.