TOPO II

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Introductions

Type II topoisomerase (TOPO II) are topoisomerases that cut both strands of the DNA helix simultaneously to manage DNA tangles and supercoils. They utilize the hydrolysis of ATP, unlike type I topoisomerases. Topoisomerases are ubiquitous enzymes, found in all organisms. In animals, topoisomerase II is a target of chemotherapy. In prokaryotes, gyrase is an antibacterial target. In fact, these enzymes have an intriguingly wide range of actions.

Figure 1. Type II topoisomerase.

Structure

TOPO II consists of two homologous subunits, each consisting of an N-terminal DNA-binding domain, a central catalytic domain, and a C-terminal ATPase structural domain, respectively. This enzyme-like molecule is highly conserved and is widely present not only in mammalian cells but also similarly present in eukaryotes and prokaryotes. The subunits interact with each other through the N-terminal domain to form a tetrameric structure, and this tetrameric structure plays a crucial role in the enzyme activity.

Classification

There are two subclasses of TOPO IIs, type IIA and IIB.

• Type IIA topoisomerases include the enzymes DNA gyrase, eukaryotic topoisomerase II (topo II), and bacterial topoisomerase IV (topo IV). These enzymes span all domains of life and are essential for function.
• Type IIB topoisomerases are structurally and biochemically distinct, and comprise a single family member, topoisomerase VI (topo VI). Type IIB topoisomerases are found in archaea and some higher plants.

Mechanism

TOPO II solves DNA strand intercalation problems during DNA replication and transcription. It is capable of breaking single or multiple interleavings on DNA and rejoining two DNA strands, thus eliminating DNA superhelical tension and being responsible for DNA slowing down. In addition, TOPO II is involved in biological processes such as chromatin restructuring, DNA recombination and repair.

Applications

TOPO II has a wide range of applications in medical research and drug development. It is widely used in cancer therapy because of its ability to inhibit the proliferation of tumor cells and induce apoptosis. A variety of chemical drugs targeting TOPO II as well as natural product-based drugs have been developed and are widely used in clinical practice. For example, cisplatin, etoposide and other commonly used chemotherapeutic drugs kill cancer cells by inhibiting TOPO II. In addition, TOPO II is also used in fields such as genetic engineering and agricultural production. It is widely used in gene cloning, preparation of transgenic plants, DNA sequencing, and other fields. By changing the expression or activity of TOPO II, precise control of transcriptional and post-transcriptional gene regulation can be achieved, thus improving the efficiency and yield of bioprocesses.

Clinical significance

TOPO II plays an important role in the development and treatment of tumors and other diseases. Various studies have shown that abnormal expression of TOPO II is closely associated with tumorigenesis and progression. Some studies have also found that the expression level of TOPO II is much higher in some tumor cells than in normal cells, suggesting that TOPO II may be an important regulator of tumor cell proliferation. In addition, some genetic mutations may also lead to abnormal expression of TOPO II, which may cause congenital diseases, such as oncogenic developmental diseases and leukodystrophy.

Conclusions

TOPO II is an enzymatic molecule with a very complex function and plays a crucial role in the process of DNA replication and transcription. It has a wide range of applications not only in medical research and drug development, but also plays an important role in fields such as genetic engineering and agricultural production. Although existing research has broken through many barriers, there are still many problems that need to be further explored and solved.