REGULATION OF THE ENDO CELL CYCLE IN DROSOPHILA

果蝇内细胞周期的调节

基本信息

项目摘要

Cell division must be regulated precisely, because when this regulation fails uncontrolled division and cancer ensue. During the development of multicellular organisms cell growth and division have to be coordinated with developmental signals. In addition to exit from the cell cycle to permit differentiation, a variety of cell cycle variants are utilized throughout the plant and animal kingdoms. One of these modified cell cycles, the endo cell cycle, results in DNA replication in the absence of mitosis and produces the polyploid or polytene cells that are found in at least some tissues in almost all organisms. This proposal addresses the three key aspects of how the endo cycle is regulated, using Drosophila as a model. The most significant distinction between the endo cycle and the mitotic cycle is the absence of mitosis. The morula gene is required to inhibit mitosis in the endo cycle. The MORULA protein will be identified and the mechanism by which it blocks mitosis determined. A second difference between the two cell cycles is that DNA replication is differentially regulated in the endo cycle such that some genomic regions are underreplicated while others are overreplicated and the genes amplified. Mutations in the two subunits of the E2F transcription factor, dDP and dE2F, affect differential replication during polyploid S phase. These results reveal a previously unrecognized role for E2F in controlling DNA replication once S phase has initiated. It will be determined whether E2F affects DNA replication via one of its transcriptional targets or whether it has a more direct effect on replication origins. Because the regulatory hierarchy that controls E2F activity is mutated in most human tumors, it is significant for understanding the causes of caner to determine how E2F influences DNA replication. The third level of regulation is common to both the endo cell cycle and the mitotic cycle: the transcripts that are induced at the G1-S transition must be downregulated after DNA replication has initiated in order for a subsequent round of replication to occur. The l(2)52Ec gene is unusual in being necessary both for DNA replication and downregulation of G1-S transcripts, suggesting it is a prerequisite for the cell to recognize that replication has initiated. The hypothesis that the l(2)51Ec protein is a component of the origin complex and necessary for downregulation of previously induced genes will be tested.
细胞分裂必须受到精确的调节,因为当这种调节失败时,不受控制的分裂和癌症随之而来。 在多细胞生物的发育过程中,细胞的生长和分裂必须与发育信号相协调。 除了从细胞周期中退出以允许分化之外,在整个植物和动物界中利用了各种细胞周期变体。 这些修饰的细胞周期之一,内细胞周期,导致在没有有丝分裂的情况下进行DNA复制,并产生在几乎所有生物体的至少一些组织中发现的多倍体或多线细胞。 该提案以果蝇为模型,阐述了endo循环如何调节的三个关键方面。 内周期和有丝分裂周期之间最显著的区别是没有有丝分裂。 桑椹胚基因是抑制内循环中有丝分裂所必需的。 将鉴定MORPHOSPHATE蛋白,并确定其阻断有丝分裂的机制。 两个细胞周期之间的第二个差异是,DNA复制在内循环中受到差异性调节,使得一些基因组区域复制不足,而另一些基因组区域复制过度并且基因扩增。 E2 F转录因子的两个亚基dDP和dE 2F中的突变影响多倍体S期期间的差异复制。 这些结果揭示了一个以前未被认识的作用E2 F在控制DNA复制一旦S期已经启动。 将确定E2 F是否通过其转录靶点之一影响DNA复制,或者它是否对复制起点具有更直接的影响。 由于控制E2 F活性的调节层次在大多数人类肿瘤中发生突变,因此确定E2 F如何影响DNA复制对于理解癌症的原因具有重要意义。 第三个水平的调控是共同的两个细胞周期和有丝分裂周期:在G1-S转换诱导的转录必须下调后,DNA复制已经开始,以进行下一轮的复制发生。 l(2)52 Ec基因是DNA复制和G1-S转录下调所必需的,这是不寻常的,表明它是细胞识别复制已经开始的先决条件。 假设l(2)51 Ec蛋白是起源复合物的一个组成部分,并且是下调先前诱导的基因所必需的,将进行测试。

项目成果

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Terry L. ORR-WEAVER其他文献

Terry L. ORR-WEAVER的其他文献

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{{ truncateString('Terry L. ORR-WEAVER', 18)}}的其他基金

Producing, provisioning, and protecting the egg: Regulation of DNA replication, mRNA translation, and proteolysis for the transition from oocyte to embryo
卵子的生产、供应和保护:从卵母细胞到胚胎过渡的 DNA 复制、mRNA 翻译和蛋白水解的调节
  • 批准号:
    9253418
  • 财政年份:
    2016
  • 资助金额:
    $ 24.49万
  • 项目类别:
Producing, provisioning, and protecting the egg: Regulation of DNA replication, mRNA translation, and proteolysis for the transition from oocyte to embryo
卵子的生产、供应和保护:从卵母细胞到胚胎过渡的 DNA 复制、mRNA 翻译和蛋白水解的调节
  • 批准号:
    9071147
  • 财政年份:
    2016
  • 资助金额:
    $ 24.49万
  • 项目类别:
Regulation of Glial Cell Size
神经胶质细胞大小的调节
  • 批准号:
    9474231
  • 财政年份:
    2015
  • 资助金额:
    $ 24.49万
  • 项目类别:
Regulation of Glial Cell Size
神经胶质细胞大小的调节
  • 批准号:
    9272447
  • 财政年份:
    2015
  • 资助金额:
    $ 24.49万
  • 项目类别:
Regulation of Glial Cell Size
神经胶质细胞大小的调节
  • 批准号:
    8942144
  • 财政年份:
    2015
  • 资助金额:
    $ 24.49万
  • 项目类别:
Regulation of the endo cell cycle in Drosophila
果蝇内细胞周期的调节
  • 批准号:
    6740174
  • 财政年份:
    1999
  • 资助金额:
    $ 24.49万
  • 项目类别:
REGULATION OF THE ENDO CELL CYCLE IN DROSOPHILA
果蝇内细胞周期的调节
  • 批准号:
    6386957
  • 财政年份:
    1999
  • 资助金额:
    $ 24.49万
  • 项目类别:
Differential DNA Replication in Drosophila Development
果蝇发育中的差异DNA复制
  • 批准号:
    8071619
  • 财政年份:
    1999
  • 资助金额:
    $ 24.49万
  • 项目类别:
Differential DNA Replication in Drosophila Development
果蝇发育中的差异DNA复制
  • 批准号:
    8466980
  • 财政年份:
    1999
  • 资助金额:
    $ 24.49万
  • 项目类别:
Regulation of the endo cell cycle in Drosophila
果蝇内细胞周期的调节
  • 批准号:
    6620001
  • 财政年份:
    1999
  • 资助金额:
    $ 24.49万
  • 项目类别:

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