Mechanism Apoptotic DNA fragmentation

a nucleosome, consisting of dna (grey) wrapped around histone tetramer (coloured). in apoptotic dna fragmentation, dna cleaved in internucleosomal linker region, part of dna not wrapped around histones.

cad cleaves dna @ internucleosomal linker sites between nucleosomes, protein-containing structures occur in chromatin @ ~180-bp intervals. because dna tightly wrapped around histones, core proteins of nucleosomes. linker sites parts of dna strand exposed , accessible cad.

degradation of nuclear dna nucleosomal units 1 of hallmarks of apoptotic cell death. occurs in response various apoptotic stimuli in wide variety of cell types. molecular characterization of process identified specific dnase (cad, caspase-activated dnase) cleaves chromosomal dna in caspase-dependent manner. cad synthesized of icad (inhibitor of cad), works specific chaperone cad , found complexed icad in proliferating cells. when cells induced undergo apoptosis, caspase 3 cleaves icad dissociate cad:icad complex, allowing cad cleave chromosomal dna. cells lack icad or express caspase-resistant mutant icad not show dna fragmentation during apoptosis, although exhibit other features of apoptosis , die.

even though work has been performed on analysis of apoptotic events, little information available link timing of morphological features @ cell surface , in nucleus biochemical degradation of dna in same cells. apoptosis can initiated myriad of different mechanisms in different cell types, , kinetics of these events vary widely, few minutes several days depending on cell system. presence or absence of particular apoptotic event(s), including dna fragmentation, depends on time window @ kinetic process of apoptosis being investigated. may complicate identification of apoptotic cells if cell populations analyzed @ single time point e.g. after induction of apoptosis.