CAD (caspase-activated DNase), a 40kDa nuclear protein, is primarily responsible for cell-autonomous DNA degradation during apoptosis. CAD is present in healthy cells where it is held in an inactive state through the association with its inhibitor ICAD. The ICAD protein is inactivated in apoptotic cells via caspase-3 cleavage thereby releasing CAD, which subsequently cleaves chromosomal DNA. CAD is a magnesium-dependent endonuclease specific for double stranded DNA that generates double strand breaks with 3'-hydroxyl ends. The nuclease preferentially attacks chromatin in the internucleosomal linker DNA. However, the nuclease hypersensitive sites can be detected and CAD is potentially involved in largescale DNA fragmentation as well. CADmediated DNA fragmentation triggers chromatin condensation that is another hallmark of apoptosis.