A patient receiving chemotherapy for small cell lung cancer develops DNA double strand breaks in tumour cells because of failure of religation of cleaved strands. The drug used targets which enzyme?

• A Proliferating cell nuclear antigen (PCNA)
• B DNA primase
• C DNA ligase I
• D DNA topoisomerase II ✓

Explanation

Etoposide stabilises the cleavable complex of eukaryotic DNA topoisomerase II with DNA, preventing religation of the double strand break the enzyme creates to relieve torsional strain. This leads to accumulation of double strand breaks and apoptosis in rapidly dividing tumour cells. Primase synthesises RNA primers, DNA ligase seals nicks, and PCNA is a sliding clamp for polymerase processivity; none create the break that this drug traps.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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