Apoptotic DNA fragmentation

[7] CAD cleaves DNA at internucleosomal linker sites between nucleosomes, protein-containing structures that occur in chromatin at ~180-bp intervals.

The presence or absence of particular apoptotic event(s), including DNA fragmentation, depends on the "time window" at which the kinetic process of apoptosis is being investigated.

[8] In 1972, Kerr, Wyllie, and Currie coined the term apoptosis and distinguished this type of cell death from necrosis based on morphological features.

[9] In 1973, Hewish and Burgoyne, during the study of subchromatin structure, found that chromatin is accessible to the Ca++/Mg++ endonuclease, resulting in the formation of a digestion product with a regular series of molecular weight similar to the one previously described by Williamson (1970).

However, this observation was without indication of "whether the incision attack on the DNA molecule was a random or rather at a particular site, that have structural or functional meaning".

[12] Six years passed from 1972 to 1978/1980 until the discovery and evaluation of internucleosomal fragmentation of DNA during apoptotic cell death as a hallmark of apoptosis.

In 1980, Wyllie reported additional evidence for an internucleosomal DNA cleavage pattern as a specific feature of glucocorticoid-treated thymocytes undergoing apoptosis.

[2] The internucleosomal DNA cleavage pattern was observed as a specific feature of apoptosis in 1978/1980 and has become a recognised hallmark of programmed cell death since then.

Apoptotic DNA fragmentation is also analyzed using agarose gel electrophoresis to demonstrate a "ladder" pattern at ~180-BP intervals.