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首页> 外文期刊>Molecular and Cellular Biology >Control of DNA Replication and Chromosome Ploidy by Geminin and Cyclin A
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Control of DNA Replication and Chromosome Ploidy by Geminin and Cyclin A

机译：Geminin和细胞周期蛋白A控制DNA复制和染色体倍性

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Alteration of the control of DNA replication and mitosis is considered to be a major cause of genome instability. To investigate the mechanism that controls DNA replication and genome stability, we used the RNA silencing-interference technique (RNAi) to eliminate the Drosophila geminin homologue from Schneider D2 (SD2) cells. Silencing of geminin by RNAi in SD2 cells leads to the cessation of mitosis and asynchronous overreplication of the genome, with cells containing single giant nuclei and partial ploidy between 4N and 8N DNA content. The effect of geminin deficiency is completely suppressed by cosilencing of Double parked (Dup), the Drosophila homologue of Cdt1, a replication factor to which geminin binds. The geminin deficiency-induced phenotype is also partially suppressed by coablation of Chk1/Grapes, indicating the involvement of Chk1/Grapes in the checkpoint control in response to overreplication. We found that the silencing of cyclin A, but not of cyclin B, also promotes the formation of a giant nucleus and overreplication. However, in contrast to the effect of geminin knockout, cyclin A deficiency leads to the complete duplication of the genome from 4N to 8N. We observed that the silencing of geminin causes rapid downregulation of Cdt1/Dup, which may contribute to the observed partial overreplication in geminin-deficient cells. Analysis of cyclin A and geminin double knockout suggests that the effect of cyclin A deficiency is dominant over that of geminin deficiency for cell cycle arrest and overreplication. Together, our studies indicate that both cyclin A and geminin are required for the suppression of overreplication and for genome stability in Drosophila cells.
机译：DNA复制和有丝分裂控制的改变被认为是基因组不稳定的主要原因。为了研究控制DNA复制和基因组稳定性的机制，我们使用了RNA沉默干扰技术（RNAi）从Schneider D2（SD2）细胞中消除了果蝇geminin同源物。 RNAi使SD2细胞中的双精蛋白沉默，从而导致有丝分裂的停止和基因组的异步过度复制，其中的细胞含有单个巨核，DNA含量在4N至8N之间。双重停泊（Dup）是Cdt1的 Drosophila 同源物，它是双倍体结合的复制因子，因此双倍停泊（Dup）的共沉默可完全抑制双倍体缺乏症的影响。 Gekin缺乏症诱导的表型也可以通过Chk1 / Grapes的消融来部分抑制，这表明Chk1 / Grapes参与了对复制过度的检查点控制。我们发现沉默细胞周期蛋白A，而不是沉默细胞周期蛋白B，也会促进巨核的形成和过度复制。但是，与基因双蛋白敲除的效果相反，细胞周期蛋白A缺乏会导致基因组从4N完全复制到8N。我们观察到geminin的沉默导致Cdt1 / Dup的快速下调，这可能有助于在geminin缺陷的细胞中观察到部分过度复制。对细胞周期蛋白A和双精蛋白双敲除的分析表明，在细胞周期停滞和过度复制中，细胞周期蛋白A缺乏症的影响高于双胞胎蛋白缺乏症。总之，我们的研究表明，细胞周期蛋白A和胚芽蛋白都需要抑制果蝇果蝇细胞中的过度复制和基因组稳定性。

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