Topoisomerase

Definition

Topoisomerase is an enzyme that plays a crucial role in managing DNA supercoiling during processes such as DNA replication, transcription, and recombination. By introducing temporary breaks in the DNA strands, topoisomerases can relieve the torsional strain that builds up ahead of the replication fork or during other DNA transactions, ensuring that the DNA strands can be separated and replicated efficiently.

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 and require ATP to do so.
2. During DNA replication, topoisomerases prevent the formation of knots and tangles that can arise from the unwinding of DNA ahead of the replication fork.
3. Eukaryotic cells contain several different topoisomerases, each with specific roles in managing DNA structure and topology.
4. Inhibitors of topoisomerases are commonly used as chemotherapy agents because they can prevent cancer cells from properly replicating their DNA.
5. Mutations in topoisomerase genes can lead to genomic instability, contributing to various diseases including cancer.

Review Questions

• How does topoisomerase facilitate DNA replication in eukaryotic cells?
  • Topoisomerase facilitates DNA replication by alleviating the torsional strain created when the double helix unwinds at the replication fork. As helicase unwinds the DNA strands, supercoiling occurs ahead of the fork, which can impede replication. Topoisomerase acts by creating temporary breaks in the DNA strands, allowing them to rotate and relieve the tension before resealing the breaks. This action ensures that replication proceeds smoothly without interruptions caused by excessive supercoiling.
• What are the differences between Type I and Type II topoisomerases, and how do these differences impact their function during DNA processes?
  • Type I topoisomerases cut one strand of the DNA helix and allow it to rotate around the intact strand to relieve supercoiling, while Type II topoisomerases cut both strands simultaneously and typically introduce negative supercoils. This fundamental difference impacts their function; Type I is often involved in relaxing supercoiled regions during replication and transcription, while Type II is crucial for separating intertwined DNA molecules during replication and chromosome segregation. The choice of which type to use is dictated by the specific needs of the cellular process underway.
• Evaluate the role of topoisomerases in maintaining genomic stability and their potential implications in cancer therapy.
  • Topoisomerases are essential for maintaining genomic stability by managing DNA supercoiling and preventing tangles during critical cellular processes like replication and transcription. When these enzymes malfunction due to mutations or become inhibited by drugs, it can lead to genomic instability, which is a hallmark of cancer. In cancer therapy, drugs that target topoisomerases are utilized because they disrupt DNA replication in rapidly dividing cancer cells. This selective targeting aims to kill cancer cells while sparing normal cells, highlighting both the critical role of topoisomerases in cellular health and their potential as therapeutic targets.

Related terms

DNA Replication Fork: The area where the double-stranded DNA splits into two single strands, allowing for new complementary strands to be synthesized.

Supercoiling: The over- or under-winding of a DNA strand, which can create tension and affect the ability of the DNA to be accessed for replication or transcription.

Helicase: An enzyme that unwinds the DNA double helix ahead of the replication fork, separating the two strands so they can be copied.