通过协调DNA双链断裂的R循环分辨率,MePCE促进同源重组
Sravan K Devanathan1, Yi-Ru Li2, Samantha B Shelton1
1Department of Molecular Biosciences, University of Texas at Austin, 2500 Speedway, Austin, TX 78712, USA.
Cell reports
|May 24, 2025
概括
MePCE蛋白通过与DNA双链断裂 (DSB) 因子相互作用来调节DNA修复. 它的耗尽损害了同源重组修复,并影响了R循环处理,解释了BRCA1缺陷的合成致死性.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 生物化学 生物化学
背景情况:
- MePCE 蛋白调节转录延长因子 P-TEFb 分区.
- 它在染色质功能,特别是DNA修复中的作用尚不清楚.
- 7SK核糖核蛋白复合体 (RNPc) 涉及到MePCE和LARP7.7. 这两种蛋白质.
研究的目的:
- 研究MePCE对染色质的功能,特别是DNA双链断裂 (DSB) 修复.
- 阐明MePCE与R循环处理和DNA修复因子的相互作用.
- 了解MePCE在DSB的7SK RNPc动态背景中的作用.
主要方法:
- 调查了MePCE对DSB的招聘情况.
- 评估了MePCE耗尽对同源重组 (HR) 修复的影响.
- 在DSB中分析了RAD51负载和R循环水平.
- 检查了与R循环处理因子和LARP7.7的相互作用.
主要成果:
- MePCE被招募到DSB中,并与DNA修复因子相互作用.
- 耗尽MePCE会损害HR,减少RAD51负载,并增加DSB的R循环水平.
- MePCE的耗尽改变了LARP7与R循环的相互作用,导致其被BRCA1/BARD1.1降解.
- 在DSB中发现了7SK RNPc的动态调节.
结论:
- MePCE在DSB通过同源重组修复中发挥着至关重要的作用.
- 在DSB中MePCE的功能涉及R循环处理和与BRCA1/BARD1通路的相互作用.
- 这些发现解释了MePCE和BRCA1缺陷之间观察到的合成致命性.
相关概念视频
Homologous Recombination
52.9K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
52.9K
Mismatch Repair
5.2K
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
5.2K
Fixing Double-strand Breaks
12.9K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.9K
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
Nucleotide Excision Repair
3.9K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.9K
Crossing Over
4.8K
Crossing over is the exchange of genetic information between homologous chromosomes during prophase I of meiosis I. Genetic recombination gives rise to allelic diversity in the newly formed daughter cells. In humans, crossing over produces genetically distinct haploid egg and sperm cells that undergo fertilization to produce unique offspring. Before cell division starts, the germ cell’s chromosome(s) undergo duplication in the S phase of the cell cycle. As the cells enter prophase I,...
4.8K


