Topoisomerase

Definition

Topoisomerase is an enzyme that helps manage the torsional strain and supercoiling that occurs in DNA during processes like replication and transcription. These enzymes play a crucial role by introducing transient breaks in the DNA strands, allowing them to unwind and alleviate stress, which is essential for the proper functioning of DNA-related processes.

5 Must Know Facts For Your Next Test

1. Topoisomerases are classified into two main types: Type I topoisomerases, which cut one strand of DNA, and Type II topoisomerases, which cut both strands.
2. Type II topoisomerases, such as DNA gyrase in bacteria, introduce negative supercoils into DNA, which helps counteract positive supercoiling during replication.
3. These enzymes are essential for preventing tangling and knotting of DNA, which can occur when the double helix is unwound.
4. Inhibitors of topoisomerases are used in cancer treatment because they can induce DNA damage in rapidly dividing cells.
5. Topoisomerases also play a role in chromatin remodeling and gene regulation by influencing DNA accessibility and structure.

Review Questions

• How do topoisomerases assist in the process of DNA replication, particularly in relation to the unwinding of the double helix?
  • Topoisomerases assist in DNA replication by relieving the torsional strain that builds up ahead of the replication fork as the double helix is unwound by helicase. When the strands are separated, they can become overly twisted or supercoiled. Topoisomerases cut the DNA strands to allow them to unwind, reducing strain and ensuring that replication proceeds smoothly without tangling or breaking.
• Discuss the differences between Type I and Type II topoisomerases and their specific roles during DNA replication.
  • Type I topoisomerases cut one strand of the DNA helix and allow it to rotate around the unbroken strand, thereby relaxing supercoiling. In contrast, Type II topoisomerases cut both strands of the DNA helix and can introduce negative supercoils into the DNA. This difference is crucial because Type II topoisomerases are particularly important in bacteria where they help manage supercoiling during rapid replication, while Type I topoisomerases are more involved in relaxing already supercoiled structures.
• Evaluate how inhibitors of topoisomerases can be utilized as therapeutic agents in cancer treatment.
  • Inhibitors of topoisomerases are valuable in cancer treatment because they target rapidly dividing cells. By blocking the function of these enzymes, these inhibitors induce DNA damage that cannot be repaired, leading to cell death. This mechanism is particularly effective against cancer cells, which often replicate at a much faster rate than normal cells. The use of topoisomerase inhibitors highlights how understanding molecular mechanisms can lead to targeted therapies that exploit specific cellular processes for therapeutic benefit.

Related terms

DNA helicase: An enzyme that unwinds the double-stranded DNA during replication, separating the strands to allow for copying.

DNA ligase: An enzyme that joins together Okazaki fragments on the lagging strand during DNA replication, sealing nicks in the sugar-phosphate backbone.

Supercoiling: The over- or under-winding of a DNA strand, which affects its topology and can impact various biological processes.