DNA topoisomerase type I (single strand cut, ATP-independent) activity

Definition

Target type: molecularfunction

Catalysis of a DNA topological transformation by transiently cleaving one DNA strand at a time to allow passage of another strand; changes the linking number by +1 per catalytic cycle. [PMID:8811192]

DNA topoisomerase type I (single strand cut, ATP-independent) activity is an essential enzyme involved in the regulation of DNA topology, playing a crucial role in various cellular processes such as DNA replication, transcription, and recombination. Its primary function is to relieve torsional stress in DNA by transiently breaking and rejoining one strand of the DNA double helix. This process involves the following steps:

1. **DNA Binding:** The enzyme binds to DNA and identifies a specific sequence where it will cleave the DNA strand.
2. **Strand Cleavage:** The enzyme uses a tyrosine residue in its active site to break a phosphodiester bond in one strand of the DNA, creating a transient single-strand break. The broken end of the DNA is held by the enzyme, preventing the broken ends from diffusing away.
3. **Strand Passage:** The enzyme allows the intact strand of DNA to pass through the break, relieving the torsional stress.
4. **Strand Religation:** The enzyme reseals the break in the DNA strand, restoring the original double-stranded structure.

This process is ATP-independent, meaning it does not require energy from ATP hydrolysis to function. Instead, the enzyme relies on the energy stored in the DNA supercoiling to drive the strand passage.

Topoisomerase I plays a critical role in various cellular processes:

* **DNA Replication:** During DNA replication, the unwinding of the DNA helix creates positive supercoiling ahead of the replication fork. Topoisomerase I relieves this supercoiling by introducing negative supercoils, allowing the replication machinery to progress.
* **Transcription:** Transcription also creates torsional stress in DNA, which can hinder the progression of RNA polymerase. Topoisomerase I alleviates this stress by removing positive supercoils, facilitating efficient transcription.
* **DNA Recombination:** DNA recombination requires the unwinding and re-joining of DNA strands. Topoisomerase I contributes to this process by resolving the topological constraints that arise during strand exchange.

Mutations or deficiencies in Topoisomerase I can lead to various cellular dysfunctions, including genomic instability, impaired DNA replication, and impaired transcription. This can contribute to various diseases, including cancer.

In summary, DNA topoisomerase type I (single strand cut, ATP-independent) activity plays a vital role in maintaining the topological state of DNA, ensuring proper DNA replication, transcription, and recombination, ultimately contributing to the integrity of the genome.'
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Proteins (1)

Compounds (54)