Etoposide, a chemotherapeutic agent used in lung cancer and lymphomas, inhibits topoisomerase II. Which best describes the normal function of topoisomerase II that is disrupted by this drug?

• A Relieves torsional strain by introducing single-strand breaks in DNA
• B Removes RNA primers and fills the resulting gaps with DNA
• C Unwinds the DNA double helix at the replication fork using ATP hydrolysis
• D Introduces double-strand breaks, passes another DNA duplex through, and reseals the break ✓

Explanation

Topoisomerase II introduces a transient double-strand break in one DNA duplex, passes another segment of DNA through the break, and then reseals it, thereby decatenating intertwined chromosomes and relieving supercoiling. Etoposide stabilizes the cleavable complex, preventing resealing and causing persistent double-strand breaks. Topoisomerase I introduces single-strand breaks, helicase unwinds DNA, and DNA polymerase I removes primers.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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