在将RAD51与DNA和染色质分离时,FIGNL1的分子基础
Alexander Carver1,2,3, Tai-Yuan Yu4,3, Luke A Yates1,2
1DNA Processing Machines Laboratory, Francis Crick Institute, London, UK.
bioRxiv : the preprint server for biology
|July 29, 2024
概括
纤维细胞生长因子INDUCIBLE 1 (FIGNL1) 蛋白质防止RAD51蛋白质在损伤后在DNA上持续存在. 这项研究揭示了FIGNL1.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学 是一个
- 结构生物学 结构生物学
背景情况:
- 基因组完整性对于预防突变和疾病至关重要.
- RAD51复合酶通过在DNA上形成细丝,在DNA修复中发挥关键作用.
- 必须严格控制RAD51发光线的形成,以避免基因毒性.
研究的目的:
- 阐明FIGNL1调节RAD51.1.的分子机制.
- 了解FIGNL1-介导的RAD51光纤拆卸的结构基础.
- 研究FIGNL1在维持基因组稳定中的作用.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定FIGNL1-RAD51复合物的结构.
- 局部定向突变发生,以评估FIGNL1残留物的功能.
- 小鼠胚胎干细胞 (mESC) 活力测试.
主要成果:
- FIGNL1形成一个非平面的六合体,将RAD51的N端包围在它的孔内.
- 在FIGNL1的孔环或催化残留物中发生的突变会影响RAD51发光线的拆卸.
- 导线拆卸中的有缺陷的FIGNL1在mESC中是致命的.
结论:
- FIGNL1使用一种独特的机制从DNA中去除RAD51.
- 对FIGNL1功能的结构洞察力为其在基因组稳定中的作用提供了分子基础.
- 针对FIGNL1可能为基因组不稳定性相关疾病提供新的治疗策略.
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
Homologous Recombination
50.4K
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...
50.4K
Disassembly of Intermediate Filaments
2.1K
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type...
2.1K
Fixing Double-strand Breaks
12.5K
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...
12.5K
Nucleosome Remodeling
9.1K
Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
9.1K
Inheritance of Chromatin Structures
6.2K
Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
6.2K


