细胞周期依赖的EBNA1-DNA交叉链接促进在ORIP和病毒插曲维护时的复制终止
Jayaraju Dheekollu1, Andreas Wiedmer1, Kasirajan Ayyanathan1
1The Wistar Institute, Philadelphia, PA, USA.
Cell
|January 22, 2021
概括
爱斯坦-巴尔病毒蛋白EBNA1在复制原点形成DNA交叉链接,这对于维护病毒插件至关重要. 这种依赖于氨酸的交叉连接涉及DNA裂变,对于病毒复制和细胞转化至关重要.
科学领域:
- 病毒学
- 分子生物学
- 表观遗传学
背景情况:
- 爱斯坦-巴尔病毒 (EBV) 是一种致癌的人类疹病毒.
- 在宿主细胞中以多副本的形式存在.
- 病原体的维持依赖于EBNA1,一个DNA结合蛋白.
研究的目的:
- 调查EBNA1介导的病变维护机制.
- 确定EBNA1在病毒DNA复制中的作用.
- 描述EBNA1与EBV复制源 (oriP) 之间的相互作用.
主要方法:
- 细胞周期分析
- DNA-蛋白交联测定 (体外和体内)
- 复制分叉分析
- 西部涂抹
主要成果:
- EBNA1与oriP形成细胞周期依赖的DNA交叉链接.
- EBNA1 的氨酸518 (Y518) 对于 oriP 交叉连接和环节维护至关重要.
- 在 oriP 端需要 Y518 进行复制分叉.
- 在复制终点处表现出单链内核酶活性.
结论:
- 在 oriP 中形成依赖于氨酸的 DNA 蛋白交叉链接.
- 这种交叉连接涉及单链DNA分裂,对于复制终止至关重要.
- 这些发现揭示了维护和复制病毒病原体的新机制.
相关概念视频
Replication in Eukaryotes
16.1K
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...
16.1K
Replication in Eukaryotes
187.7K
Overview
187.7K
Restarting Stalled Replication Forks
6.1K
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,...
6.1K
Homologous Recombination
59.2K
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...
59.2K
The DNA Replication Fork
38.9K
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...
38.9K
The DNA Replication Fork
17.2K
17.2K


