Topoisomerase

Definition

Topoisomerases are enzymes that regulate the overwinding or underwinding of DNA during replication and transcription. By introducing or removing twists in the DNA helix, they help maintain the proper supercoiling necessary for cellular processes, ensuring that DNA remains accessible for replication and transcription while preventing tangles and knots.

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 to relieve tension, and Type II topoisomerases, which cut both strands and can introduce negative supercoils.
2. These enzymes are crucial during DNA replication, as they prevent supercoiling from hindering the progression of the replication fork.
3. Topoisomerase inhibitors are used as chemotherapy agents in cancer treatment because they can prevent cancer cells from successfully replicating their DNA.
4. In bacteria, topoisomerase IV helps separate intertwined daughter chromosomes after DNA replication, ensuring proper cell division.
5. Topoisomerases play a role in various cellular processes beyond replication, including transcription and chromosome segregation during cell division.

Review Questions

• How do topoisomerases contribute to the process of DNA replication?
  • Topoisomerases contribute to DNA replication by managing the tension created as the DNA double helix unwinds. During replication, the helicase enzyme separates the two strands of DNA, leading to supercoiling ahead of the replication fork. Topoisomerases alleviate this stress by introducing or removing twists in the DNA strand, ensuring that the replication machinery can function smoothly without getting tangled.
• Compare and contrast Type I and Type II topoisomerases in terms of their mechanisms and functions.
  • Type I topoisomerases operate by cleaving one strand of the DNA duplex to relieve torsional stress and allow rotation around the intact strand. They typically relax positive supercoils. In contrast, Type II topoisomerases cut both strands of the DNA helix and can introduce negative supercoils. This difference in mechanism allows Type II enzymes to resolve more complex supercoiling situations during processes like replication and chromosome segregation.
• Evaluate the significance of topoisomerase inhibitors in cancer treatment and discuss their mechanism of action.
  • Topoisomerase inhibitors are significant in cancer treatment because they target rapidly dividing cells, which rely heavily on effective DNA replication. By inhibiting topoisomerases, these drugs prevent proper relaxation and separation of DNA strands during replication. This leads to accumulation of DNA breaks and ultimately triggers apoptosis in cancer cells. Understanding how these inhibitors work can provide insight into designing targeted therapies that disrupt cancer cell proliferation while minimizing effects on normal cells.

Related terms

DNA supercoiling: A structural feature of DNA where the double helix is twisted beyond its normal coiling, impacting processes like replication and transcription.

Chromatin: The complex of DNA and proteins found in eukaryotic cells that packages DNA into a more compact, dense shape, influencing gene expression.

Nucleosome: The fundamental unit of chromatin, consisting of a segment of DNA wound around a core of histone proteins, helping to organize and compact the DNA.