用复制叉进行TOP3A合,并修复TOP3A裂解复合体
Liton Kumar Saha1, Yves Pommier1
1Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.
Cell cycle (Georgetown, Tex.)
|February 11, 2024
概括
人类拓酶IIIα (TOP3A) 对于线粒体和核中的DNA复制至关重要. 了解 TOP3A 的理解
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生物化学
背景情况:
- 人类具有两种IA型拓酶:拓酶IIIα (TOP3A) 和拓酶IIIβ (TOP3B).
- TOP3A在DNA复制中起着至关重要的作用,影响核和线粒体DNA过程.
研究的目的:
- 审查了解人类TOP3A在DNA复制过程中的功能方面的最新进展.
- 探索TOP3A链接DNA断裂和DNA-蛋白质交叉链的形成,修复和影响.
主要方法:
- 审查有关拓酶功能和DNA复制的现有文献.
- 分析TOP3A介导的DNA裂变和重新密封的机制.
- 对TOP3A-DNA复合体的DNA修复途径的讨论.
主要成果:
- TOP3A通过可逆的DNA链分离和重组来管理DNA拓的功能.
- TOP3A可以形成稳定的分裂复合体 (TOP3Accs) 和具有DNA断裂的DNA-蛋白交叉链接 (TOP3A-DPCs).
- TOP3A-DPC修复通路的缺陷与基因组不稳定性,神经疾病和线粒体疾病有关.
结论:
- 在DNA复制过程中,TOP3A对于保持基因组完整性至关重要.
- 不可逆转的TOP3Acc和TOP3A-DPC对基因组稳定性构成重大威胁.
- 高效修复TOP3A-DPCs对于预防相关疾病至关重要.
相关概念视频
Restarting Stalled Replication Forks
5.8K
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,...
5.8K
Homologous Recombination
50.5K
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...
50.5K
DNA Topoisomerases
31.3K
Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. These enzymes regulate positive and negative DNA supercoiling without changing the nucleotide sequence. DNA overwinding in a clockwise direction results in positively supercoiled DNA, whereas underwinding in a counterclockwise direction produces negatively supercoiled DNA.
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
31.3K
The DNA Replication Fork
36.0K
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...
36.0K
Translesion DNA Polymerases
10.0K
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...
10.0K
Fixing Double-strand Breaks
12.6K
The double-stranded structure of DNA has two major advantages. First, it serves as a safe repository of genetic information where one strand serves as the back-up in case the other strand is damaged. Second, the double-helical structure can be wrapped around proteins called histones to form nucleosomes, which can then be tightly wound to form chromosomes. This way, DNA chains up to 2 inches long can be contained within microscopic structures in a cell. A double-stranded break not only damages...
12.6K


