Cyclin G is involved in meiotic recombination repair in Drosophila melanogaster
Cyclin G is involved in meiotic recombination repair in Drosophila melanogaster
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DOI：
10.1242/jcs.113902
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发表时间：
2012-11-15
影响因子：
4
通讯作者：
Preiss, Anette
中科院分区：
文献类型：
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作者：
Nagel, Anja C.;Fischer, Patrick;Preiss, Anette
细胞周期蛋白G（CycG）属于非典型细胞周期蛋白，具有多种细胞功能。两种哺乳动物CycG基因CycG 1和CycG 2调节细胞周期以响应细胞应激。由于缺乏突变体，对果蝇cycG基因的作用的详细分析受到阻碍。我们在果蝇cycG基因中产生了一个无效突变体，它是雌性不育的，并产生腹侧化的卵。这种表型是卵子发生过程中表皮生长因子受体（EGFR）信号转导下调的典型表现。在减数分裂DNA双链断裂修复缺陷的突变体（例如纺锤体类的突变体）中也观察到受精卵。双链断裂（DSB）通过激活Mei-41激酶（果蝇ATR同源物）诱导减数分裂检查点，从而间接导致背腹图案缺陷。我们提供的证据，CycG在减数分裂检查点控制的作用。在cycG突变体中DSB发生率的增加可能反映了DSB修复效率低下。因此，下调Mei-W 68（一种诱导减数分裂DSB的核酸内切酶）、Mei-41或黑腹果蝇Chk 2（一种启动减数分裂检查点的下游激酶）拯救了cycG突变型蛋壳表型。在体内，CycG与Rad 9和BRCA 2相关。这两种蛋白质是9-1-1复合物的组分，其参与感测DSB和激活减数分裂检查点控制。因此，我们认为CycG在减数分裂重组修复的早期步骤中发挥作用，从而影响卵子发生过程中EGFR介导的模式化过程。
Cyclin G (CycG) belongs to the atypical cyclins, which have diverse cellular functions. The two mammalian CycG genes, CycG1 and CycG2, regulate the cell cycle in response to cell stress. Detailed analyses of the role of the single Drosophila cycG gene have been hampered by the lack of a mutant. We generated a null mutant in the Drosophila cycG gene that is female sterile and produces ventralised eggs. This phenotype is typical of the downregulation of epidermal growth factor receptor (EGFR) signalling during oogenesis. Ventralised eggs are also observed in mutants (for example, mutants of the spindle class) that are defective in meiotic DNA double-strand break repair. Double-strand breaks (DSBs) induce a meiotic checkpoint by activating Mei-41 kinase (the Drosophila ATR homologue), thereby indirectly causing dorsoventral patterning defects. We provide evidence for the role of CycG in meiotic checkpoint control. The increased incidence of DSBs in cycG mutant germaria may reflect inefficient DSB repair. Therefore, the downregulation of Mei-W68 (an endonuclease that induces meiotic DSBs), Mei-41, or Drosophila melanogaster Chk2 (a downstream kinase that initiates the meiotic checkpoint) rescues the cycG mutant eggshell phenotype. In vivo, CycG associates with Rad9 and BRCA2. These two proteins are components of the 9-1-1 complex, which is involved in sensing DSBs and in activating meiotic checkpoint control. Therefore, we propose that CycG has a role in an early step of meiotic recombination repair, thereby affecting EGFR-mediated patterning processes during oogenesis.