循环E/CDK2和可溶性基因组蛋白的反调节了基因组生物合成的S相爆发
Claire Armstrong1, Victor J Passanisi1, Humza M Ashraf1
1Department of Biochemistry, University of Colorado Boulder, Boulder, CO 80303, USA; BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
Cell reports
|July 10, 2023
概括
细胞精确地控制着用于DNA复制的质子的产生. 在G1/S过渡时,由CDK2-介导的NPAT酸化触发的基因组mRNA的爆发,确保了足够的基因组用于DNA合成.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 忠实地复制DNA需要精确调节组织素水平,这对于包装新合成的DNA至关重要.
- 歇斯顿生物合成与细胞循环有关,在G1/S过渡时发生了显著的增加,但基本的调节机制仍然不完全理解.
研究的目的:
- 阐明控制在G1/S阶段过渡期间激素生物合成爆发的分子机制.
- 为了研究细胞如何调节与DNA复制协调的组 histone 生产.
主要方法:
- 使用单细胞时间延迟成像来观察整个细胞周期中的组素生产动态.
- 生物化学分析被用来识别关键的调节蛋白和酸化事件.
主要成果:
- 在限制点对NPAT的CDK2-介导的酸化被确定为启动基因组转录的触发因素.
- 在G1/S阶段边界观察到基因组mRNA的精确爆发,与DNA复制的开始相吻合.
- 发现积累的可溶性组 histone 蛋白在 S 阶段诱导组 histone mRNA 降解,防止过度生产.
结论:
- 细胞中质子的产生受到两种不同的协同作用机制的严格调节:在G1/S阶段的转录激活和在S阶段的转录后降解.
- 这种双重调控系统确保了DNA复制的适当的组素可用性,并保持了基因组的完整性.
相关概念视频
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Positive Regulator Molecules
5.5K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K
The Cell Cycle Control System
3.1K
The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and...
3.1K
Molecular Factors Affecting Cell Division
3.2K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.2K
Negative Regulator Molecules
35.5K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.5K
DNA Damage can Stall the Cell Cycle
9.2K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
9.2K


