Apoptosis, DNA fragmentation factor 40kDa (IPR015311)

Short name: Apoptosis_DFF40

Overlapping homologous superfamilies


Domain relationships



Apoptosis, or programmed cell death (PCD), is a common and evolutionarily conserved property of all metazoans [PMID: 11341280]. In many biological processes, apoptosis is required to eliminate supernumerary or dangerous (such as pre-cancerous) cells and to promote normal development. Dysregulation of apoptosis can, therefore, contribute to the development of many major diseases including cancer, autoimmunity and neurodegenerative disorders. In most cases, proteins of the caspase family execute the genetic programme that leads to cell death.

DNA fragmentation factor (DFF) is a complex of the DNase DFF40 (CAD) and its chaperone/inhibitor DFF45 (ICAD-L). In its inactive form, DFF is a heterodimer composed of a 45kDa chaperone inhibitor subunit (DFF45 or ICAD), and a 40kDa latent endonuclease subunit (DFF40 or CAD). Upon caspase-3 cleavage of DFF45, DFF40 forms active endonuclease homo-oligomers. It is activated during apoptosis to induce DNA fragmentation. DNA binding by DFF is mediated by the nuclease subunit, which can also form stable DNA complexes after release from DFF [PMID: 17626049, PMID: 15572351]. The nuclease subunit is inhibited in DNA cleavage but not in DNA binding [PMID: 15572351]. DFF45 can also be cleaved and inactivated by caspase-7 but not by caspase-6 and caspase-8. The cleaved DFF45 fragments dissociate from DFF40, allowing DFF40 to oligomerise, forming a large complex that cleaves DNA by introducing double strand breaks. Histone H1 confers DNA binding ability to DFF and stimulates the nuclease activity of DFF40 [PMID: 10318789].

GO terms

Biological Process

GO:0006309 apoptotic DNA fragmentation

Molecular Function

GO:0016787 hydrolase activity

Cellular Component

GO:0005737 cytoplasm
GO:0005634 nucleus

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.