复制识别器将表观遗传和代谢途径与复制应激反应联系起来
Sophie C van der Horst1, Leonie Kollenstart1,2, Amandine Batté1
1Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
Nature communications
|February 6, 2025
概括
研究人员使用一种名为复制识别器 (Repli-ID) 的新方法确定了423个调节DNA复制的基因. 该工具跟踪酵母突变体中的DNA聚合酶epsilon (Pol ε),揭示了参与复制应激反应的LGE1和ROX1等关键蛋白质.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 细胞生物学 细胞生物学
背景情况:
- DNA复制对于细胞分裂至关重要,其干扰可能导致复制叉停滞或崩.
- 一个复杂的复制应激反应网络存在,以稳定分叉和激活检查点,但许多参与的蛋白质仍然未知.
研究的目的:
- 开发一种全基因组的方法来识别DNA复制的调节者.
- 发现参与细胞对复制应激反应的新型蛋白质和途径.
主要方法:
- 复制识别器 (Repli-ID) 的开发,该技术将染色体免疫沉 (ChIP) 与下一代测序相结合.
- 追踪复制性聚合酶epsilon (Pol ε) 在成千上万的基尿素治疗酵母突变体中复制的条形码来源.
主要成果:
- 鉴定了423个在复制分叉中促进Pol ε结合的基因,包括LGE1和ROX1.
- 机械洞察:Lge1通过H2B单一无处不在影响复制启动/稳定性;Rox1通过陶胺水平影响分叉进展,S阶段进入和检查点激活.
结论:
- 复制ID是发现DNA复制调节者的强大资源.
- 该研究阐明了LGE1和ROX1在复制压力下维持基因组稳定性的新角色.
相关概念视频
The DNA Replication Fork
35.4K
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...
35.4K
Restarting Stalled Replication Forks
5.7K
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,...
5.7K
Replication in Eukaryotes
13.0K
In eukaryotic cells, DNA replication is highly conserved and tightly regulated. Multiple linear chromosomes must be duplicated with high fidelity before cell division, so there are many proteins that fulfill specialized roles in the replication process. Replication occurs in three phases: initiation, elongation, and termination, and ends with two complete sets of chromosomes in the nucleus.
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
Many Proteins Orchestrate Replication at the Origin
Eukaryotic replication follows many of the same...
13.0K
S-Cdk Initiates DNA Replication
4.6K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.6K
DNA Damage can Stall the Cell Cycle
9.0K
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...
9.0K
Chromosome Replication
8.6K
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...
8.6K


