毒素可以防止由Myc瘤基因引起的复制性压力
Silvia Sberna1, Marco Filipuzzi1, Nicola Bianchi1
1Center for Genomic Science of IIT, CGS@SEMM (Istituto Italiano di Tecnologia at European School of Molecular Medicine), Fondazione Istituto Italiano di Tecnologia (IIT), 20139, Milan, Italy.
Cell death & disease
|March 20, 2025
概括
RNA螺旋酶SENATAXIN (SETX) 能够防止由瘤性Myc.引起的复制性压力. 失去SETX会引发DNA损伤和细胞死亡,为Myc驱动的癌症提供潜在的治疗点.
科学领域:
- 分子瘤学分子瘤学
- 在DNA损伤和修复过程中.
- RNA生物学的RNA生物学
背景情况:
- 复制性压力 (RS) 是癌症的一个关键治疗目标.
- 了解预防RS的机制对于治疗开发至关重要.
- 众所周知,瘤性Myc可以诱导RS.
研究的目的:
- 调查RNA螺旋酶Senataxin (SETX) 在预防Myc诱导的复制性压力的作用.
- 探索SETX作为Myc驱动癌症的潜在治疗标.
主要方法:
- 研究了Myc激活癌细胞中的SETX功能.
- 利用RNA干扰来使SETX沉默.
- 进行了ATR通路激酶的药理抑制.
- 分析了DNA损伤反应 (DDR) 的参与.
- 绘制的DNA双链断裂全基因组范围.
- 在特定的基因组位置检查了R环形成.
主要成果:
- 沉默SETX选择性地激活了DNA损伤反应 (DDR),并在Myc激活时引起细胞毒性.
- 抑制ATR通路增强了SETX介导的DDR.
- 失去SETX导致DDR焦点和新复制区域的R循环增加,而不是全基因组.
- 由于SETX缺乏,转录复制冲突 (TRC) 区域的DNA损伤加剧,特别是在早期复制的部位.
结论:
- SETX解决了阻碍复制机制的转录相关R循环,从而防止Myc诱导的TRC和复制应激.
- 在瘤性Myc驱动的瘤中,SETX是一种遗传负担,呈现出一种新的治疗策略.
更多相关视频
相关概念视频
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
Induced Pluripotent Stem Cells
3.9K
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...
3.9K
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
Abnormal Proliferation
4.4K
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...
4.4K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
The DNA Replication Fork
35.3K
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...
35.3K


