对于哺乳动物细胞中有效的复制动力学,Srcap染色体重塑器是必需的
Stefka K Dzhokova1, Rossitsa H Hristova1, Peter S Botev1
1Roumen Tsanev Institute of Molecular Biology, Bulgarian Academy of Sciences, Acad. G. Bonchev Str. 21, 1113 Sofia, Bulgaria.
International journal of molecular sciences
|December 30, 2025
概括
染色体重塑器Srcap对于DNA复制至关重要. 它通过组织色素和维护复制基因,确保有效的复制叉进展和起源发射.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- 与SNF2相关的染色体改造器Srcap在调节区域沉积了组分离子变异H2A.Z,影响了转录.
- Srcap在DNA复制中的作用以前没有被研究过.
研究的目的:
- 为了研究Srcap在哺乳动物细胞中DNA复制中的作用.
- 阐明Srcap通过哪些机制影响复制分叉的进展和原始点火.
主要方法:
- 在人类PC3细胞中进行RNA干扰 (RNAi),以耗尽Srcap.
- 测量复制叉的延长率和密度.
- 对复制压力标志物 γH2AX.X 的分析.
- 高分辨率膨胀显微镜可视化复制焦点.
- 已公布数据的转录学分析.
主要成果:
- Srcap 枯竭使复制叉的延长率降低了 ~25%,并降低了叉密度.
- Srcap缺乏导致γH2AX增加和染色质结合的H2A.Z.减少.
- 扩展显微镜显示复制焦点强度降低,间距增加,表明源激活减少.
- 转录组数据显示,在Srcap损失时,复制相关基因的下调.
结论:
- Srcap对于有效的DNA复制至关重要,它协调了分叉的进展和原始点火.
- Srcap通过一种双重机制起作用,涉及H2A.Z依赖的染色质组织和复制机制的转录维护.
- 通过调节复制动态,Srcap在维持基因组稳定性方面发挥着至关重要的作用.
相关概念视频
Nucleosome Remodeling
10.7K
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...
10.7K
Chromatin Modification in iPS Cells
2.1K
Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...
2.1K
Chromosome Replication
10.4K
Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins. This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
10.4K
Restarting Stalled Replication Forks
6.2K
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,...
6.2K
Duplication of Chromatin Structure
7.1K
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
7.1K
The Replisome
37.9K
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...
37.9K


