DNA复制检查点限制了Okazaki碎片的积累,以保护和重新启动停滞不前的分叉
Berta Canal1, Agostina P Bertolin1, Giselle C Lee1
1Chromosome Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
Molecular cell
|June 27, 2025
概括
细胞DNA复制分叉在核酸枯竭下停滞不前. 一个DNA复制检查点通过限制蛋白质封存和保护停滞的分叉免于崩来防止基因组不稳定,确保重新启动.
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:
- 基因复制对于基因组的稳定性至关重要.
- 复制叉的崩导致遗传不稳定性和癌症.
- 了解分叉停滞和重启机制至关重要.
研究的目的:
- 为了重建DNA复制叉停滞和重启使用纯化的芽酵母蛋白质.
- 为了阐明在停滞叉的复制检查点控制背后的分子机制.
主要方法:
- 在体外复制DNA复制分叉的重建停滞并重新启动.
- 使用纯化的开花酵母蛋白质.
- 研究了DNA复制检查点的作用.
主要成果:
- 核酸枯竭停止了领先链的合成,但CMG基酶继续解.
- 不完整的奥卡扎基碎片封存复制蛋白 (PCNA,RFC,DNA聚合酶d和e).
- DNA复制检查点抑制了分叉的进展,防止了蛋白质的封存,并保护了停滞的分叉.
结论:
- DNA复制检查点在维持基因组稳定性方面发挥着至关重要的作用.
- 通过检查点控制叉子的进展对于防止叉子崩和确保重新启动至关重要.
- 这项研究提供了复制叉动力学和检查点调节的分子细节.
相关概念视频
Restarting Stalled Replication Forks
5.9K
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,...
5.9K
The DNA Replication Fork
36.9K
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...
36.9K
DNA Damage can Stall the Cell Cycle
9.3K
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...
9.3K
The Replisome
35.0K
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...
35.0K
Translesion DNA Polymerases
10.2K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.2K
The Spindle Assembly Checkpoint
3.3K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.3K


