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What prevents topoisomerase?

What prevents topoisomerase?

Topoisomerase I poisons are more widely used than temozolomide and DTIC in the treatment of cancer. Topoisomerase I reduces the torsional strain in DNA resulting from local unwinding for replication and transcription by forming a transient complex with DNA catalysing the cleavage, unwinding and relegation of DNA.

What happens if DNA topoisomerase is inhibited?

Topoisomerase inhibitors influence these essential cellular processes. These topoisomerase-DNA-inhibitor complexes are cytotoxic agents, as the un-repaired single and double stranded DNA breaks that they cause can lead to apoptosis and cell death.

What would happen if topoisomerase was defective Why?

Topoisomerase alleviates supercoiling downstream of the origin of replication. In the absence of topoisomerase, supercoiling tension would increase to the point where DNA could fragment. DNA replication could not be initiated because there would be no RNA primer. DNA strands would not be ligated together.

How does topoisomerase affect DNA replication?

Type II topoisomerases change DNA topology by breaking and rejoining double-stranded DNA. Topoisomerases are important both in growing fork movement and in resolving (untangling) finished chromosomes after DNA duplication. Both replicated circular and linear DNA chromosomes are separated by type II topoisomerases.

Why is topoisomerase not needed in PCR?

The sequence specificity of the primers is what limits DNA replication to the desired region of DNA and nowhere else. Helicase and topoisomerase are not needed to unwind and release tension in DNA, their jobs are accomplished by a combination of high temperature and the short length of the DNA being amplified.

Which of the following inhibits the action of topoisomerases?

Topoisomerase inhibitors in current use in the United States include irinotecan and topotecan, inhibitors of topoisomerase I, and etoposide and teniposide, inhibitors of topoisomerase II. All four agents are semisynthetic analogues of natural toxins that were initially identified in plants.

Which of the following drugs inhibits bacterial topoisomerase?

Fluoroquinolones. Fluoroquinolones inhibit bacterial cell proliferation by inhibiting DNA gyrase and topoisomerase IV, both essential enzymes in bacterial DNA transcription and replication (Hooper, 2001).

What would happen if topoisomerase is not available for DNA replication?

(a) If topoisomerase was not available for DNA replication the strands would not be able to relieve the tension created by helicase untwisting them. This may destabilize the strand and prevent binding and proper manipulation by other replication enzymes.

Why is topoisomerase needed in DNA replication?

Topoisomerase also plays an important maintenance role during DNA replication. This enzyme prevents the DNA double helix ahead of the replication fork from getting too tightly wound as the DNA is opened up.

Can topoisomerase break covalent bonds?

Topoisomerase breaks a covalent bond in the backbone of one parental strand. ( Topoisomerase relieves the strain caused by unwinding of the DNA by helicase.

How does inhibition of topoisomerases cause cell death?

Inhibition of DNA topoisomerases by small molecules is an effective method for causing DNA damage due to the formation of irreversible covalent cross-links between the topoisomerase and DNA, stalling its replication and thereby leading to cell death.

Why is Topoisomerase important to the integrity of DNA?

This is to help limit the time in which the integrity of the DNA may be compromised. However, the topoisomerase DNA complex can become trapped, forming a stalled Top-DNA adduct, otherwise known as an abortive Top complex.

How does the topoisomerase inhibitor camptothecin work?

Treatment with TopI inhibitors stabilizes the intermediate cleavable complex, preventing DNA re-ligation, and inducing lethal DNA strand breaks. Camptothecin -derived TopI inhibitors function by forming a ternary complex with TopI-DNA and are able to stack between the base pairs that flank the cleavage site due to their planar structure.

What are the different types of topoisomerase inhibitors?

Type II topoisomerase inhibitors. These inhibitors are split into two main classes: topoisomerase poisons, which target the topoisomerase-DNA complex, and topoisomerase inhibitors, which disrupt catalytic turnover.

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