key term - Topoisomerases

Definition

Topoisomerases are enzymes that play a crucial role in managing DNA supercoiling and torsional strain during processes such as DNA replication and repair. They achieve this by introducing transient breaks in the DNA strands, allowing for the relaxation of supercoiled regions, and then resealing the breaks. This action is essential for maintaining the integrity and accessibility of the DNA during critical cellular functions.

5 Must Know Facts For Your Next Test

1. Topoisomerases are classified into two types: Type I topoisomerases, which cut one strand of the DNA, and Type II topoisomerases, which cut both strands.
2. During DNA replication, topoisomerases help alleviate the tension that builds up ahead of the replication fork as the DNA unwinds.
3. These enzymes are also involved in DNA repair processes, ensuring that any supercoiling resulting from damage is resolved.
4. Inhibitors of topoisomerases are often used as chemotherapy agents because they can prevent cancer cells from properly replicating their DNA.
5. Topoisomerases play a significant role in both prokaryotic and eukaryotic cells, highlighting their importance across different forms of life.

Review Questions

• How do topoisomerases function during DNA replication, and why is their activity critical at the replication fork?
  • Topoisomerases function by introducing temporary breaks in the DNA strands to alleviate the torsional strain that occurs when DNA is unwound at the replication fork. As helicase unwinds the double helix, it creates positive supercoiling ahead of the fork, which could hinder replication. By cutting one or both strands, topoisomerases allow for relaxation of this supercoiling before resealing the breaks, ensuring smooth progression of DNA replication.
• What distinguishes Type I topoisomerases from Type II topoisomerases in their mechanism of action?
  • Type I topoisomerases work by cutting one strand of the DNA double helix to relieve supercoiling and do not require ATP for their activity. In contrast, Type II topoisomerases cut both strands of the DNA simultaneously, allowing another segment of DNA to pass through before resealing the breaks. This fundamental difference in their mechanism allows Type II enzymes to manage more complex supercoiling situations, particularly during high-stress events like DNA replication and transcription.
• Evaluate the implications of topoisomerase inhibitors in cancer treatment and how they exploit cellular processes related to DNA replication.
  • Topoisomerase inhibitors are significant in cancer treatment because they disrupt the normal function of these enzymes during DNA replication in rapidly dividing cancer cells. By preventing topoisomerases from relieving torsional strain, these inhibitors lead to increased DNA damage and ultimately cell death. This strategy exploits the fact that cancer cells often have heightened reliance on efficient DNA replication for proliferation. Therefore, targeting topoisomerases serves as an effective means to halt cancer progression by taking advantage of their essential roles in cellular processes.

Related terms

DNA helicase:

An enzyme that unwinds the DNA double helix, separating the two strands to allow for replication and transcription.

DNA ligase:

An enzyme that connects and seals gaps between DNA fragments during replication and repair processes.

Nucleotide excision repair:

A DNA repair mechanism that removes damaged or mispaired nucleotides, allowing for accurate restoration of the DNA sequence.