酵母端粒的损失:停止,恢复和染色体损失
1Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Cell
|November 19, 1993
概括
酵母端粒对于区分完整的染色体和受损的DNA至关重要. 它们的缺失会触发细胞循环停止,但也会导致显著的染色体不稳定和损失,即使修复系统活跃.
科学领域:
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 端粒保护染色体末端免受降解和融合.
- 细胞检查点,如RAD9通路,检测DNA损伤以防止异常细胞分裂.
研究的目的:
- 研究端粒在维持染色体稳定性和细胞周期调节中的作用.
- 了解酵母模型中端粒损失的后果.
主要方法:
- 在可用染色体上构建具有单个可消除端粒的酵母菌株.
- 在端粒切除后观察细胞循环停止和染色体损失.
- 对染色体稳定性和分离后端粒损失的分析.
主要成果:
- 端粒消除诱导了RAD9介导的细胞循环停止,标志着端粒在DNA损伤识别中的作用.
- 许多细胞从停止中恢复过来,但缺少端粒的染色体显示出损失的急剧增加.
- 缺少端粒的染色体被复制并分离了最多10个部分,然后最终丢失.
结论:
- 酵母端粒对于DNA损伤信号和长期染色体稳定性都至关重要.
- 检查点和修复机制不足以防止丢失端粒的染色体丢失.
- 端粒完整性对于防止基因组不稳定性至关重要.
相关概念视频
Replication in Eukaryotes
Overview
Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
Replicative Cell Senescence
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 the telomeric...
Loss of Tumor Suppressor Gene Functions
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Replication in Eukaryotes
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.


