During apoptosis, DNA fragmentation into nucleosomal multiples of 180 base pairs produces the characteristic 'DNA ladder' on gel electrophoresis. Which enzyme, activated downstream of executioner caspases, mediates this cleavage?
- A Endonuclease G released directly from mitochondria without caspase involvement
- B Caspase-activated DNase (CAD), freed after cleavage of its inhibitor ICAD ✓
- C PARP-1 acting as a nuclease after automodification
- D DNase II operating in the acidic lysosomal compartment
Correct answer: B. Caspase-activated DNase (CAD), freed after cleavage of its inhibitor ICAD
Explanation
Executioner caspases (mainly caspase-3) cleave the inhibitor of caspase-activated DNase (ICAD/DFF45), releasing CAD, which enters the nucleus and cuts internucleosomal linker DNA into 180 bp multiples. PARP is itself a substrate cleaved by caspase-3 as a marker of apoptosis, not the nuclease. Endonuclease G contributes in some settings but the classic ladder is attributed to CAD activation.
Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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