What a CAD!

Here, as promised, is just one example of how caspases can wreak havoc on the cell. Believe it or not, your cells make enzymes called DNAases that can destroy your DNA. One such DNAase is the enzyme CAD, or Caspase-Activated-DNAase. Thankfully, this enzyme is synthesized along with its own inhibitor, the Inhibitor of CAD or ICAD. ICAD keeps CAD inactive in the cytoplasm--until caspases get activated. Caspases can cleave ICAD, which exposes the CAD enzyme. CAD's nuclear localization signal directs the enzyme to the nucleus, where it cuts the chromosomal DNA between the nucleosomes.

Animation. How caspase activation can lead to destruction of DNA. Basically, this is a wipe of the hard drive--a biothermodynamic black hole. Once this happens, the cell cannot recover.

In this way, CAD generates nucleosomal fragments of DNA. A single nucleosomal stretch of DNA is 200 base pairs (bp) long. Since the CAD may not cut between every single nucleosome, it produces fragments in a range of molecular weights that are multiples of 200 bp--200, 400, 600, and so on. This is the source of the DNA Laddering that we mentioned earlier, which was classically considered a hallmark of apoptosis. If you take tissue or cells that are undergoing apoptosis and run them out on a gel that separates molecules by their molecular weight, you'll get that "ladder" of fragments, all at multiples of 200 bp. 

 

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