检查点激酶通过影响染色体动态来调节DNA损伤后的昼夜时钟
Yulin Yang1,2, Zeyu Duan1, Xiao-Lan Liu1
1State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Nucleic acids research
|March 7, 2025
概括
检查点激酶CHK1/2通过调节染色质结构来维持DNA损伤期间的昼夜节律. 这些激酶确保节奏基因转录,这对应激下细胞健康至关重要.
科学领域:
- 时间生物学 时间生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 生物钟,细胞周期和DNA修复之间的关系是已知的.
- 通过DNA损伤反应对昼夜钟的表观遗传调节的理解较少.
研究的目的:
- 研究检查点激酶在DNA损伤期间对昼夜节律的表观遗传控制中的作用.
- 阐明DNA损伤反应维持昼夜节律的机制.
主要方法:
- 使用Neurospora crassa作为一个模型生物.
- 进行了基因删除研究 (chk1/2).
- 分析了基因转录,蛋白质结合 (WCC),染色质结构和基因组修饰 (H3T11酸化,H3乙化,H2A.Z沉积).
- 进行了全基因组相关性分析和转录组分析.
主要成果:
- 在DNA损伤下删除CHK1/2破坏了时钟基因frq的节律转录.
- CHK1/2通过促进H3T11酸化和H3乙化来调节frq促进者的染色质结构,抵消H2A.Z沉积.
- 在DNA损伤期间,CHK1/2对代谢和DNA修复基因的节奏转录至关重要.
结论:
- 检查点激酶CHK1/2在DNA损伤压力下保持稳健的昼夜节律中起着至关重要的作用.
- CHK1/2协调表观遗传修饰,以确保适合昼夜基因表达的染色质状态.
- 这项研究揭示了一种新的机制,将DNA损伤反应途径与生理时钟调节联系起来.
相关概念视频
DNA Damage can Stall the Cell Cycle
9.0K
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...
9.0K
Circadian Rhythms and Gene Regulation
4.0K
The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
4.0K
Negative Regulator Molecules
35.1K
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.
35.1K
Inhibition of Cdk Activity
4.6K
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...
4.6K
The Cell Cycle Control System
2.5K
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...
2.5K
DNA Damage Can Stall the Cell Cycle
2.6K
2.6K


