Agarose gel electrophoresis of DNA extracted from a population of dying lymphocytes shows a characteristic ladder pattern of fragments in multiples of approximately 180 base pairs. Which nuclease produces this pattern, and how is it regulated?

• A Endonuclease G, released from mitochondria by BAX pores
• B DNase II, activated by lysosomal rupture during necrosis
• C TREX1 exonuclease, activated by STING pathway signaling
• D Caspase-activated DNase, held inactive by ICAD until caspase-3 cleaves ICAD ✓

Explanation

Executioner caspase-3 cleaves inhibitor of caspase-activated DNase (ICAD), releasing CAD, which degrades chromatin between nucleosomes, yielding internucleosomal fragments of roughly 180 bp multiples and producing the classic DNA ladder. Endonuclease G also escapes mitochondria during apoptosis but is not the canonical basis of the ladder taught in standard texts, and random smearing rather than laddering characterizes necrotic DNA breakdown.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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