核细胞体是S阶段内检查点的关键目标,用于应对复制应激
Xiaoqin Liu1,2, Bo Zhang1, Yu Hua1
1Peking-Tsinghua Center for Life Sciences, The National Laboratory of Protein and Plant Gene Research, College of Life Sciences, Peking University, Beijing 100871, China.
Science advances
|May 16, 2025
概括
在S相内检查点的目标是Brl2泛基因酶,降低基因素泛基因化和压缩色素以稳定停滞的DNA复制分叉. 这种规则可以防止DNA断裂和叉子崩.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 内部S相检查点对于保持DNA复制叉稳定性至关重要.
- 这个检查站的精确监管机制尚未完全理解.
- 了解这些机制是理解基因组稳定性的关键.
研究的目的:
- 确定S阶段内检查点的关键目标.
- 为了阐明在检查点调节中的ubiquitin E3结合酶 Brl2的作用.
- 调查Brl2活动如何影响染色质结构和DNA修复.
主要方法:
- 在复制叉停滞时,通过Cds1Chk2激酶研究了Brl2酸化.
- 使用brl2-5D和htb-K119R突变来评估染色体紧缩.
- 对比不同突变菌株的复制叉崩和DNA断裂的比率.
主要成果:
- 通过Cds1Chk2的Brl2酸化使其结合酶活性失活,并降低H2BK119ub1水平.
- Brl2或H2BK119的突变会在停滞的分叉中破坏染色质分解.
- Brl2功能的丧失显著降低了复制的崩和∆细胞中的DNA断裂.
结论:
- 在S相内检查点通过Brl2准核体,以在停滞的复制分叉中建立紧的染色质结构.
- 这种染色体重塑对于防止复制叉崩和DNA损伤至关重要.
- 结果提供了关于ATR/Chk1与ATM激酶的差异实质性的见解.
相关概念视频
Chromosome Replication
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 of...
The DNA Replication Fork
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 forks, one in...
Restarting Stalled Replication Forks
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, a...
S-Cdk Initiates DNA Replication
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 replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
The DNA Replication Fork
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 forks, one in...
S-Cdk Initiates DNA Replication
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 replication.
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.


