Fragmentation (cell Biology) - Apoptosis

Apoptosis

Apoptosis refers to the demise of cells by programmed cell death, marked by a well-defined sequence of morphological changes. Cellular and nuclear shrinkage, chromatin condensation and fragmentation, formation of apoptotic bodies and phagocytosis by neighboring cells characterize the main morphological changes in the apoptosis process. Extensive morphological and biochemical changes during apoptosis ensure that dying cells leave minimal impact on neighboring cells and/or tissues.

Genes involved in controlling cell death encode proteins with three distinct functions:

• "Killer" proteins are required for a cell to begin the apoptotic process
• "Destruction" proteins do things such as digest DNA in a dying cell
• "Engulfment" proteins are required for phagocytosis of the dying cell by another cell

The cleavage of chromosomal DNA into smaller fragments is an integral part, and biochemical hallmark, of apoptosis. Apoptosis involves the activation of endonucleases with subsequent cleavage of chromatin DNA into fragments of 180 base pairs or multiples of 180 base pairs (e.g. 360, 540). This pattern of fragmentation can be used to detect apoptosis in tests such as a DNA laddering assay with gel electrophoresis, a TUNEL assay, or a Nicoletti assay. Apoptotic DNA fragmentation relies on an enzyme called Caspase-Activated DNase (CAD). CAD is usually inhibited by another protein in the cell, called Inhibitor of caspase-activated DNase (ICAD). In order for apoptosis to begin, an enzyme called caspase 3 cleaves ICAD so that CAD becomes activated. CAD then cleaves the DNA between nucleosomes, which occur in chromatin at 180 base pair intervals. The sites between nucleosomes are the only parts of the DNA that are exposed and accessible to CAD.