基因组不稳定性是由托波异相酶功能障碍引起的
Karin C Nitiss1, Afif Bandak2, James M Berger2
1Pharmaceutical Sciences Department, University of Illinois Chicago, Rockford, IL 61107, USA.
International journal of molecular sciences
|October 16, 2024
概括
托波异相酶管理DNA拓,但如果它们的复密功能受损,则可能导致基因组不稳定. 了解这些酶对于癌症研究至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
- 生物化学 生物化学
背景情况:
- 托波异相酶通过短暂的DNA链断裂 (DSB) 调节DNA拓.
- 它们的机制涉及一个可逆的蛋白质/DNA复合体,使得快速重新密封以防止持续的DNA损伤.
- 由于小分子,DNA结构或突变造成的再密封受损会导致基因组不稳定.
研究的目的:
- 审查最近关于拓酶功能和功能障碍的研究.
- 突出拓酶在基因组不稳定性和癌症中的作用.
- 探索细胞机制,以限制topoisomerase诱导的遗传损伤.
主要方法:
- 对近期有关拓酶酶的最新研究的文献综述.
- 对I型和II型拓聚合酶的酶/DNA诱导后果的分析.
- 检查由拓酶功能失调引起的基因变异.
主要成果:
- 拓糖酶I (Top1) 对核糖核酸的作用导致了删除;突变的Top1产生了大的删除.
- 由小分子或突变准的拓二酶II (Top2) 会导致重复.
- Top1和Top2都能诱导大量的基因组重组和转移.
结论:
- 拓糖酶功能失调是一种致病机制,有助于瘤性进展.
- 了解细胞如何限制毒酶诱导的基因组不稳定性对于癌症研究至关重要.
- 在癌细胞中观察到的基因变异中,托波异相酶起着重要的作用.
相关概念视频
DNA Topoisomerases
31.0K
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. ...
31.0K
Conservative Site-specific Recombination and Phase Variation
5.9K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
5.9K
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
Nucleotide Excision Repair
3.5K
DNA Distortion and Damage
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
3.5K
Genome Copying Errors
4.2K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.2K
Microtubule Instability
5.0K
Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.0K


