核蛋白 GNL3 阻止了停滞不前的复制分叉的切割
Rana Lebdy1,2, Marine Canut1, Julie Patouillard1
1Institut de Génétique Humaine (UMR9002), CNRS, Université de Montpellier, Montpellier Cedex 5, France.
EMBO reports
|November 15, 2023
概括
人类GNL3蛋白通过控制DNA原始点火来防止复制应激期间的DNA损伤. 这一发现对于了解癌细胞基因组稳定性和病变耐受性至关重要.
科学领域:
- 分子生物学分子生物学
- 癌症生物学 癌症生物学
- 遗传学 遗传学 是一个
背景情况:
- 忠实的DNA复制依赖于保护复制叉的蛋白质,并防止损害基因组的病变.
- 了解参与DNA损伤积累和癌症耐受性的蛋白质是必不可少的.
研究的目的:
- 为了识别参与DNA复制叉保护的新型蛋白质.
- 阐明人类GNL3/核胺在复制压力期间预防DNA损伤中的作用.
主要方法:
- 研究了GNL3在应对复制压力的功能.
- 分析了DNA切除,原始点燃和蛋白质相互作用 (GNL3和ORC2).
- 利用技术来评估GNL3局部化及其对复制因子的影响.
主要成果:
- 人类GNL3在复制压力下防止新生DNA的核酶依赖切除.
- 抑制原始发射减少了DNA切除,这表明GLN3枯竭诱导的原始激活驱动了切除.
- GNL3与核中的ORC2相互作用,其核度限制了DNA切除.
结论:
- 对于限制DNA切除而言,GNL3的核细胞定位和与ORC2的相互作用至关重要.
- GNL3控制源点火,将ORC2隔离在核中,以防止在复制压力期间新生的DNA切除.
- 这种机制对于维持癌细胞基因组稳定性至关重要.
更多相关视频
08:53Strand-Specific Analysis of Proteins at Replicating DNA Strands by Enrichment and Sequencing of Protein-Associated Nascent DNA Method
Published on: May 2, 2025
371
07:37Author Spotlight: Unraveling the Dynamics of Eukaryotic DNA Replication Through Single-Molecule Visualization
Published on: September 27, 2024
1.6K
相关概念视频
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
The DNA Replication Fork
36.0K
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...
36.0K
DNA Damage can Stall the Cell Cycle
9.2K
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...
9.2K
Homologous Recombination
50.6K
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...
50.6K
The Replisome
33.6K
DNA replication is carried out by a large complex of proteins that act in a coordinated matter to achieve high-fidelity DNA replication. Together this complex is known as the DNA replication machinery or the replisome.
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
The synthesis of the leading and lagging strands is a highly coordinated process. To explain this, the “Trombone model” was proposed by Bruce Alberts in 1980. The DNA loop formation starts when a primer is synthesized on the parent lagging strand. The loop grows with...
33.6K
Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
