The Drosophila endocycle is controlled by cyclin E and lacks a checkpoint ensuring S-phase completion

The Drosophila endocycle is controlled by cyclin E and lacks a checkpoint ensuring S-phase completion
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DOI:
10.1101/gad.10.19.2514
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发表时间:
1996-10-01
影响因子:
10.5
通讯作者:
Spradling, AC
Spradling, AC
中科院分区:
生物学1区
文献类型:
--
作者:
Lilly, MA;Spradling, AC

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在果蝇卵子发生的早期,每个生殖系包囊的16个相互连接的细胞在两种不同的命运中做出选择。单个未来的卵母细胞进入减数分裂,停止,并成为转录静止。剩下的15个细胞启动一系列多倍体细胞周期,为它们作为养育细胞的角色做准备。像许多其他多倍体和多线细胞一样,在营养细胞生长过程中,主要卫星DNA由于一种仍然不清楚的机制而变得高度不足。我们牵连的细胞周期调节因子细胞周期蛋白E在DNA的代表性不足,通过确定一个亚型,女性不育cycE突变,cycE(01672),增加卫星DNA繁殖的数量在护士细胞。在突变体而非野生型有丝分裂内滋养细胞中,观察到溴脱氧尿苷掺入的“晚S”模式与有丝分裂细胞中的模式相似。CycE蛋白仍然在cycE(01672)生殖系包囊中循环,但水平降低,并且在细胞周期的较长部分中发现。我们的实验支持CycE的振荡水平控制多倍体S期的观点。此外,他们指出,连接未复制DNA的存在与CycE振荡器的检查点是缺乏的,导致不完全复制的后期复制序列,如卫星DNA。出乎意料的是,在cycE(01672)包囊中的16个细胞中有2 - 3个经常分化为卵母细胞,这暗示了卵母细胞决定中的细胞周期编程。
Early during Drosophila oogenesis the 16 interconnected cells of each germ-line cyst choose between two alternative fates. The single future oocyte enters meiosis, arrests, and becomes transcriptionally quiescent. The remaining 15 cells initiate a series of polyploid cell cycles to prepare for their role as nurse cells. Like many other polyploid and polytene cells, during nurse cell growth the major satellite DNAs become highly under-represented by a mechanism that has remained obscure. We implicate the cell-cycle regulator cyclin E in DNA under-representation by identifying a hypomorphic, female sterile cycE mutation, cycE(01672), that increases the amount of satellite DNA propagated in nurse cells. In mutant but not wild-type endomitotic nurse cells, ''late S'' patterns of bromodeoxyuridine incorporation are observed similar to those in mitotic cells. CycE protein still cycles in cycE(01672) germ-line cysts but at reduced levels, and it is found throughout a longer fraction of the cell cycle. Our experiments support the view that oscillating levels of CycE control the polyploid S phase. Moreover, they indicate that a checkpoint linking the presence of unreplicated DNA to the CycE oscillator is lacking, leading to incomplete replication of late-replicating sequences such as satellite DNAs. Unexpectedly, two to three of the 16 cells in cycE(01672) cysts frequently differentiate as oocytes, implicating cell-cycle programming in oocyte determination.