要求p53和p21在DNA损伤后维持G2逮捕
F Bunz1, A Dutriaux, C Lengauer
1The Howard Hughes Medical Institute and The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
概括
在DNA受损后,p53和p21蛋白对维持G2细胞周期检查点至关重要. 如果没有功能性p53或p21,细胞就无法正常被捕,导致细胞分裂错误.
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:
- DNA损伤会在G2阶段触发细胞循环停止,从而允许DNA修复.
- 瘤抑制蛋白p53及其下游点p21是细胞周期检查点的关键调节者.
研究的目的:
- 调查p53和p21在维持DNA损伤后G2细胞周期停止中的作用.
- 确定p53和p21对于人体细胞中适当的G2检查点功能的必要性.
主要方法:
- 在人类细胞中利用p53和p21的基因破坏.
- 使用马辐射诱导DNA损伤.
- 通过观察细胞形态和DNA含量来分析细胞周期进展和细胞动力学.
主要成果:
- 持续的G2逮捕取决于p53的存在和转录活性,该蛋白激活p21.
- 尽管DNA受损,但p53或p21基因的破坏导致过早进入线粒分裂.
- 缺乏功能性p53或p21的细胞表现出G2DNA含量,原因是细胞动力学失败,而不是适当的停止.
结论:
- 在DNA受损后,p53-p21通路对于维持人类细胞中的G2检查点至关重要.
- p53和p21对于防止异常细胞分裂和确保基因组稳定性至关重要.
相关概念视频
Negative Regulator Molecules
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.
DNA Damage can Stall the Cell Cycle
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...
Inhibition of Cdk Activity
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...
Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
DNA Damage Can Stall the Cell Cycle
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...
The Cell Cycle Control System
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 function at the cell...
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...


