Trim33掩盖了E2f4在复制分叉进展中的非转录功能
Vanessa Rousseau1,2,3, Elias Einig1, Chao Jin1
1Department of Medical Oncology and Pulmonology, University Hospital Tübingen, Otfried-Müller-Str 14, 72076, Tübingen, Germany.
Nature communications
|August 23, 2023
概括
在压力期间,Trim33-E2f4-Recql通路调节了DNA复制叉的进展. 这种机制维持了基因组的完整性,并影响了癌症的发展.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- 复制性压力是基因组不稳定性和瘤发生的关键驱动因素.
- 了解DNA复制控制途径对于治疗策略至关重要.
研究的目的:
- 阐明Trim33-E2f4-Recql轴在压力下调节DNA复制中的作用.
- 研究这种途径对基因组完整性和瘤产生的影响.
主要方法:
- 使用ubiquitination试验研究了蛋白质相互作用和降解.
- 通过药物或基因诱导的压力模型分析了DNA复制叉的进展和染色质的招募.
- 在细胞系中利用基因删除和枯竭技术,包括Myc过度表达模型.
主要成果:
- E2f4招募Recql以促进在压力下复制叉的进展.
- 在未被扰乱的细胞中,Trim33 基化酶准了 E2f4 的降解.
- 复制应激减少了Trim33依赖的无处不在,促进了E2f4-Recql相互作用和DNA合成恢复.
- 删除Trim33会在压力下加速复制,损害检查点信号和DNA修复.
- 在Myc-overexpressing细胞中,Trim33的枯竭会增加DNA损伤,并延迟瘤发生.
结论:
- Trim33-E2f4-Recql轴是DNA复制分叉进展的关键调节器,特别是在转录活性染色体上.
- 这种途径在维持基因组完整性方面发挥着重要作用,并影响了Myc驱动的瘤发生的速度.
相关概念视频
The DNA Replication Fork
36.1K
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...
36.1K
Restarting Stalled Replication Forks
5.8K
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.8K
Replication in Eukaryotes
14.0K
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...
14.0K
DNA Replication
49.8K
DNA replication involves the separation of the two strands of the double helix, with each strand serving as a template from which the new complementary strand is copied. After replication, each double-stranded DNA includes one parental or “old” strand and one “new” strand. This is known as semiconservative replication. The resulting DNA molecules have the same sequence and are divided equally into the two daughter cells.
Replication in Prokaryotes
DNA replication...
Replication in Prokaryotes
DNA replication...
49.8K
Replication in Prokaryotes
25.0K
DNA replication has three main steps: initiation, elongation, and termination. Replication in prokaryotes begins when initiator proteins bind to the single origin of replication (ori) on the cell's circular chromosome. Replication then proceeds around the entire circle of the chromosome in each direction from the two replication forks, resulting in two DNA molecules.
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
Many Proteins Work Together to Replicate the Chromosome
Replication is coordinated and carried out by a host of specialized...
25.0K
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


