Cdc14B-Cdh1-Plk1轴控制G2的DNA损伤反应检查点
Florian Bassermann1, David Frescas, Daniele Guardavaccaro
1Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.
Cell
|July 30, 2008
概括
哺乳动物细胞在DNA受损后在G2阶段激活DNA修复途径. 这涉及Cdc14B酸酶,导致Plk1降解和稳定检查点蛋白质,以有效地应对G2DNA损伤.
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:
- 哺乳动物细胞需要强大的机制来防止在G2阶段DNA损伤后进入线粒分裂.
- G2 DNA损伤反应 (DDR) 检查点对于通过停止细胞循环进展来维持基因组稳定性至关重要.
- 密解和细胞循环的关键调节者必须严格控制,以确保适当的DNA修复.
研究的目的:
- 为了阐明控制哺乳动物细胞G2DNA损伤反应的分子途径.
- 确定酸酶Cdc14B在协调细胞循环停止和DNA修复中的作用.
- 了解在G2中的基因毒性压力期间如何调节线粒激酶和检查点蛋白.
主要方法:
- 研究了Cdc14B在对基因毒性压力的反应中的亚细胞局部化和活性.
- 使用生物化学测试来分析激活阿纳促进复合体/环体 (APC/C(Cdh1) 的情况.
- 研究了线粒激酶Plk1的降解以及Claspin和Wee1.1的稳定.
- 评估了二基化酶USP28在调节Claspin稳定性和Chk1激活中的作用.
主要成果:
- 在G2中,Cdc14B在G2中的基因毒性压力下从核中转移到核质中.
- Cdc14B激活APC/C(Cdh1) 导致Plk1降解,稳定Claspin和Wee1以提供高效的G2检查点.
- Usp28对抗APC/C(Cdh1) 介导的Claspin降解,确保DNA修复的Chk1激活.
结论:
- 涉及Cdc14B,APC/C(Cdh1) 和Usp28的新途径对于G2 DNA损伤反应至关重要.
- 这一途径确保了细胞循环的停止,并通过调节关键的线粒细胞和检查点蛋白来促进DNA修复.
- 这些发现为维护DNA损伤后的基因组完整性提供了关键的见解.
相关概念视频
02:36DNA 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...
02:11The Cell Cycle Control System
The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:36DNA 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...
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
01:28The 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...