致癌性c-Myc通过增加CTCF依赖的方式增加cohesins染色质占用率来诱导复制应激
Silvia Peripolli1, Leticia Meneguello1,2, Chiara Perrod1
1Laboratory Molecular Cell Biology, University College London, Gower Street, London, UK.
Nature communications
|February 21, 2024
概括
致癌性c-Myc通过增加DNA上的凝聚素来驱动癌症,导致复制压力. 这种依赖于CTCF位点的积累阻碍了复制分叉的进展,导致了基因组的不稳定.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 基因组学就是基因组学.
背景情况:
- 瘤基因诱导的复制压力是癌症发展和基因组不稳定的关键因素.
- 产生这种压力的精确机制尚未完全理解.
- 凝聚素在DNA修复和基因组稳定性中起着已知的作用.
研究的目的:
- 为了研究凝聚素在瘤基因诱导的复制应激中的作用.
- 阐明像c-Myc这样的瘤基因对复制压力的贡献机制.
- 探索凝聚素在引起和耐受复制压力的双重作用.
主要方法:
- 研究了c-Myc对凝聚素局部化的影响.
- 在依赖CTCF的地点检查了凝聚素的积累.
- 评估了凝聚素积累对复制分叉进展的影响.
主要成果:
- 观察到DNA上的凝聚素的瘤性c-Myc-依赖的增加.
- 复制应激需要在特定的CTCF位点积聚凝聚素,而不仅仅是整体染色素.
- 这种机制独立于先前已知的瘤基因诱导的复制应激途径.
结论:
- 在CTCF位点增加的凝聚力有助于通过阻碍复制叉来导致瘤基因诱导的复制压力.
- 凝聚素表现出双重作用,既引起,又保护免受复制压力诱导的DNA损伤.
- 了解这种双重作用为癌症演变和潜在的治疗策略提供了新的见解.
更多相关视频
08:33Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
Published on: December 5, 2017
14.3K
10:11Author Spotlight: Investigating the Motion Dynamics of the Eukaryotic Replisome Components at the Single-Molecule Level
Published on: July 26, 2024
1.0K
相关概念视频
Induced Pluripotent Stem Cells
4.1K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
4.1K
Anaphase Promoting Complex
2.9K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.9K
M-Cdk Drives Transition Into Mitosis
5.6K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
5.6K
S-Cdk Initiates DNA Replication
4.7K
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...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K
Cohesins
4.5K
Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
Cohesin complexes in Meiotic Division
Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
4.5K
The DNA Replication Fork
36.0K
An organism’s genome needs to be duplicated in an efficient and error-free manner for its growth and survival. The replication fork is a Y-shaped active region where two strands of DNA are separated and replicated continuously. The coupling of DNA unzipping and complementary strand synthesis is a characteristic feature of a replication fork. Organisms with small circular DNA, such as E. coli, often have a single origin of replication; therefore, they have only two replication...
36.0K
