Type I topoisomerase

Enzyme that alters the supercoiling of DNA

Type I topoisomerase is an enzyme that plays a crucial role in the DNA replication and transcription processes by altering the supercoiling of DNA. It achieves this by creating a transient single-strand break in the DNA, allowing the DNA to unwind or rewind, and then resealing the break. This action is essential for relieving the torsional strain that builds up ahead of the replication fork and during transcription.

Function

Type I topoisomerases are responsible for cutting one strand of a DNA double helix, allowing it to rotate around the uncut strand, and then rejoining the cut strand. This process is ATP-independent, distinguishing it from Type II topoisomerases, which require ATP to function. The enzyme's ability to relax supercoiled DNA is vital for maintaining the proper structure and function of the genome.

Mechanism

The mechanism of Type I topoisomerase involves several steps:

1. Cleavage: The enzyme binds to the DNA and cleaves one of the strands, forming a covalent bond between the enzyme and the DNA.
2. Strand Passage: The uncut strand is passed through the break, allowing the DNA to relax.
3. Religation: The enzyme reseals the break, restoring the integrity of the DNA.

This process is facilitated by a tyrosine residue in the active site of the enzyme, which forms a transient covalent bond with the DNA.

Types

There are two main subtypes of Type I topoisomerases:

• Type IA topoisomerases: These enzymes relax negatively supercoiled DNA and are found in both prokaryotes and eukaryotes.
• Type IB topoisomerases: These enzymes can relax both positive and negative supercoils and are primarily found in eukaryotes.

Biological Importance

Type I topoisomerases are essential for various cellular processes, including DNA replication, transcription, and chromosome segregation. They help prevent DNA tangling and breakage, which can lead to genomic instability and mutations.

Clinical Significance

Inhibitors of Type I topoisomerases, such as camptothecin and its derivatives, are used as anticancer agents. These drugs stabilize the transient DNA-topoisomerase complex, preventing the religation step and leading to DNA damage and cell death.

Images

Structure of a Type I topoisomerase

Illustration of Type I topoisomerase action

Active site of Topoisomerase IB

Detailed view of the active site

Related pages

• DNA replication
• Transcription (biology)
• Topoisomerase
• Type II topoisomerase

References

• Wang, J.C. (1996). "DNA topoisomerases." Annual Review of Biochemistry, 65, 635-692.
• Champoux, J.J. (2001). "DNA topoisomerases: Structure, function, and mechanism." Annual Review of Biochemistry, 70, 369-413.

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  Type I topoisomerase structure

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  Type I topoisomerase

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  Topoisomerase IB active site

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  Topoisomerase IB active site