Topoisomerases

topoisomerases

Topoisomerases

topoisomerases

Topoisomerases are a group of enzymes that play a crucial role in the maintenance and regulation of DNA topology. DNA, the genetic material in cells, is a long double-stranded helix that can become highly twisted and tangled during essential cellular processes such as replication, transcription, and recombination. Topoisomerases resolve these topological problems by altering the DNA structure.

There are two main types of topoisomerases: type I and type II. Each type carries out a specific set of functions and operates through different mechanisms.

  1. Type I topoisomerases: These enzymes work by introducing transient single-strand breaks in the DNA molecule. They can either be classified as type IA or type IB based on the directionality of the strand passage:
    1. Type IA topoisomerases, such as human topoisomerase I, break one DNA strand and pass the intact strand through the break before resealing it. They are involved in relaxing supercoiled DNA and facilitating DNA replication and transcription.
    2. Type IB topoisomerases, like bacterial DNA gyrase, operate similarly to type IA enzymes, but they relax both positively and negatively supercoiled DNA. They are also involved in processes like DNA replication, transcription, and recombination.
  2. Type II topoisomerases: These enzymes are ATP-dependent and introduce double-strand breaks in the DNA molecule. They can be further classified into type IIA and type IIB:
    1. Type IIA topoisomerases, such as human topoisomerase II (also known as DNA gyrase), form a transient covalent linkage between the enzyme and the DNA molecule. They pass an intact DNA segment through another DNA double helix before resealing the break. Type IIA topoisomerases are involved in processes such as DNA replication, chromosome condensation, and decatenation (separation of interlinked DNA molecules).
    2. Type IIB topoisomerases, like human topoisomerase VI, are less well-studied compared to type IIA enzymes. They function in a manner similar to type IIA enzymes but have distinct differences in their mechanisms and cellular roles.
Overall, topoisomerases are crucial for maintaining DNA structure, resolving topological stress, and enabling various cellular processes. Their dysfunction or inhibition can have severe consequences on genome stability and cell viability. In fact, many clinically important anticancer and antibacterial drugs target topoisomerases to disrupt DNA replication and cell division, leading to cell death.

There are two main types of topoisomerases: type I and type II. Each type carries out a specific set of functions and operates through different mechanisms.

  1. Type I topoisomerases: These enzymes work by introducing transient single-strand breaks in the DNA molecule. They can either be classified as type IA or type IB based on the directionality of the strand passage:
    1. Type IA topoisomerases, such as human topoisomerase I, break one DNA strand and pass the intact strand through the break before resealing it. They are involved in relaxing supercoiled DNA and facilitating DNA replication and transcription.
    2. Type IB topoisomerases, like bacterial DNA gyrase, operate similarly to type IA enzymes, but they relax both positively and negatively supercoiled DNA. They are also involved in processes like DNA replication, transcription, and recombination.
  2. Type II topoisomerases: These enzymes are ATP-dependent and introduce double-strand breaks in the DNA molecule. They can be further classified into type IIA and type IIB:
    1. Type IIA topoisomerases, such as human topoisomerase II (also known as DNA gyrase), form a transient covalent linkage between the enzyme and the DNA molecule. They pass an intact DNA segment through another DNA double helix before resealing the break. Type IIA topoisomerases are involved in processes such as DNA replication, chromosome condensation, and decatenation (separation of interlinked DNA molecules).
    2. Type IIB topoisomerases, like human topoisomerase VI, are less well-studied compared to type IIA enzymes. They function in a manner similar to type IIA enzymes but have distinct differences in their mechanisms and cellular roles.
Overall, topoisomerases are crucial for maintaining DNA structure, resolving topological stress, and enabling various cellular processes. Their dysfunction or inhibition can have severe consequences on genome stability and cell viability. In fact, many clinically important anticancer and antibacterial drugs target topoisomerases to disrupt DNA replication and cell division, leading to cell death.

References

  • Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. Molecular Biology of the Cell (4th edition). Garland Science. Chapter 6, DNA Topology. 2002.
  • Wang, J. C. Cellular roles of DNA topoisomerases: a molecular perspective. Nature Reviews Molecular Cell Biology, 3(6), 430-440. 2002.
  • Nitiss, J. L. DNA topoisomerases in cancer chemotherapy: Using enzymes to generate selective DNA damage. Current Opinion in Investigational Drugs, 10(12), 1232-1240. 2009.
  • Nitiss, J. L. Targeting DNA topoisomerase II in cancer chemotherapy. Nature Reviews Cancer, 9(5), 338-350. 2009.

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