CGG三重重复结合蛋白1对抗R循环诱导的转录复制压力
Henning Ummethum1, Augusto C Murriello1, Marcel Werner1
1Institute of Epigenetics and Stem Cells (IES), Helmholtz Munich, Feodor-Lynen-Strasse 21, Munich, 81377, Germany.
EMBO reports
|August 26, 2025
概括
在CGG重复中防止转录复制冲突. CGGBP1的损失导致R循环积累和转录缺陷,突出显示其在基因组稳定性中的作用.
科学领域:
- 分子生物学
- 遗传学
- 表观遗传学
背景情况:
- CGG三重重复结合蛋白1 (CGGBP1) 与CGG重复结合,但其在转录和复制中的作用尚不清楚.
- 基因促进体中的短CGG重复可以形成R循环,可能破坏细胞过程.
研究的目的:
- 调查CGGBP1在CGG重复序列中的转录和复制的功能.
- 确定CGGBP1的分子合作伙伴和维持基因组稳定的机制.
主要方法:
- 对人类基因促进体中CGGBP1与CGG重复体结合的分析.
- 在CGGBP1贫乏细胞中对转录,R环形成和RNA聚合酶II (RNAPII) 活性进行评估.
- 通过共同消耗实验识别CGGBP1相互作用蛋白.
主要成果:
- 在容易形成R循环的促进体中,CGGBP1与CGG重复体结合.
- 失去了CGGBP1,导致转录放松,R循环积累和转录复制冲突 (TRC).
- CGGBP1使用DDX41和DHX15酶来解决R循环并防止TRC.
结论:
- 简短的CGG重复是基因组不稳定的二次结构的来源.
- CGGBP1及其相互作用的螺旋酶对于协调CGG重复的转录和复制至关重要.
- 保持适当的转录复制协调对于基因组稳定性至关重要.
相关概念视频
Restarting Stalled Replication Forks
5.9K
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,...
5.9K
Cooperative Binding of Transcription Regulators
6.5K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.5K
Transcription Attenuation in Prokaryotes
16.0K
Transcriptional attenuation occurs when RNA transcription is prematurely terminated due to the formation of a terminator mRNA hairpin structure. Bacteria use these hairpins to regulate the transcription process and control the synthesis of several amino acids including histidine, lysine, threonine, and phenylalanine. Transcription attenuation takes place in the non-coding regions of mRNA.
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
There are several different mechanisms used to attenuate transcription. In ribosome mediated...
16.0K
The DNA Replication Fork
36.8K
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...
36.8K
Stringent Response in E. coli
52
Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
52
Co-activators and Co-repressors
7.5K
Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
7.5K


