DNA fragmentation factor (DFF45/DFFA) is a component of DFF, the principle DNA endonuclease responsible for nucleosomal DNA cleavage during apoptosis. In the DFF complex, DFF45/DFFA heterodimerizes with DFF40 and is a substrate of the apoptotic effector, caspase 3. Initiation of the cellular apoptotic program results in the activation of caspase 3 and the cleavage and release of DFF45 from its heterodimeric partner, DFF40. The release of DFF40 from the inhibitory activity of DFF45 allows DFF40 to function as a DNA endonuclease to promote chromosomal DNA fragmentation. A 35 kDa splice variant of DFF45, DFF35, also exists and functions as a chaperone and alternative heterodimeric partner for DFF40.