Topoisomerase

Definition

Topoisomerase is an essential enzyme involved in the replication and transcription of DNA. It functions by introducing temporary breaks in the DNA backbone, allowing the strands to unwind and relieve the torsional stress that builds up during these crucial cellular processes.

5 Must Know Facts For Your Next Test

1. Topoisomerases are classified into two main types: Type I topoisomerases, which introduce single-strand breaks, and Type II topoisomerases, which introduce double-strand breaks in the DNA.
2. Topoisomerase I relieves torsional stress in DNA by creating a transient single-strand break, allowing the DNA to unwind, and then resealing the break.
3. Topoisomerase II uses the energy of ATP hydrolysis to create a temporary double-strand break, pass another segment of DNA through the break, and then reseal the break.
4. Topoisomerases are essential for DNA replication, as they help to unwind the DNA ahead of the replication fork, allowing the DNA polymerase to copy the genetic material.
5. Certain topoisomerase inhibitors, such as the chemotherapeutic drugs camptothecin and etoposide, are used in cancer treatment as they induce DNA damage and cell death in rapidly dividing cancer cells.

Review Questions

• Explain the role of topoisomerases in DNA replication.
  • Topoisomerases play a crucial role in DNA replication by relieving the torsional stress that builds up ahead of the replication fork. As the DNA unwinds and the replication process progresses, the DNA strands become increasingly supercoiled, which can impede the movement of the replication machinery. Topoisomerases, such as Topoisomerase I and Topoisomerase II, temporarily break the DNA backbone, allowing the strands to unwind and relieving the torsional stress. This enables the DNA polymerase to efficiently copy the genetic material during replication.
• Describe the differences between Type I and Type II topoisomerases and their mechanisms of action.
  • Type I topoisomerases introduce a single-strand break in the DNA, allowing the strands to rotate and relieve torsional stress, while Type II topoisomerases create a temporary double-strand break and pass another segment of DNA through the break. Type I topoisomerases, such as Topoisomerase I, use a transesterification reaction to create the single-strand break, whereas Type II topoisomerases, such as Topoisomerase II, utilize the energy of ATP hydrolysis to catalyze the double-strand break and DNA strand passage. The different mechanisms of these two topoisomerase classes allow them to play complementary roles in managing DNA topology during crucial cellular processes like replication and transcription.
• Evaluate the significance of topoisomerase inhibitors in cancer treatment and their mechanism of action.
  • Certain topoisomerase inhibitors, such as camptothecin and etoposide, are widely used in cancer chemotherapy due to their ability to induce DNA damage and cell death in rapidly dividing cancer cells. These inhibitors work by stabilizing the covalent complex formed between the topoisomerase enzyme and the DNA, preventing the enzyme from completing the DNA cleavage-religation cycle. This leads to the accumulation of persistent DNA breaks, which triggers apoptosis in the cancer cells. The selective toxicity of these topoisomerase inhibitors towards rapidly proliferating cancer cells, compared to normal cells, makes them an effective class of anticancer drugs. Understanding the mechanism of action of topoisomerase inhibitors is crucial for developing more targeted and effective cancer therapies.

Related terms

DNA Supercoiling: The coiling of DNA molecules into higher-order structures, which can create torsional stress that must be relieved for replication and transcription to occur.

DNA Unwinding: The process of separating the two strands of the DNA double helix, a necessary step for both replication and transcription to take place.

DNA Topology: The study of the spatial arrangement and properties of DNA molecules, including their degree of supercoiling and linking number.