Reactome | Apoptosis induced DNA fragmentation

Apoptosis induced DNA fragmentation

Stable Identifier

R-HSA-140342

Type

Pathway

Species

Homo sapiens

Compartment

cytosol, nucleoplasm

ReviewStatus

5/5

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DNA fragmentation in response to apoptotic signals is achieved, in part, through the activity of apoptotic nucleases, termed DNA fragmentation factor (DFF) or caspase-activated DNase (CAD) (reviewed in Widlak and Garrard, 2005). In non-apoptotic cells, DFF is a nuclear heterodimer consisting of a 45 kD chaperone and inhibitor subunit (DFF45)/inhibitor of CAD (ICAD-L)] and a 40 kD nuclease subunit (DFF40/CAD)( Liu et al. 1997, 1998; Enari et al. 1998). During apoptosis, activated caspase-3 or -7 cleave DFF45/ICAD releasing active DFF40/CAD nuclease. The activity of DFF is tightly controlled at multiple stages. During translation, DFF45/ICAD, Hsp70, and Hsp40 proteins play a role in insuring the appropriate folding of DFF40 during translation(Sakahira and Nagata, 2002). The nuclease activity of DFF40 is enhanced by the chromosomal proteins histone H1, Topoisomerase II and HMGB1/2(Widlak et al., 2000). In addition, the inhibitors (DFF45/35; ICAD-S/L) are produced in stoichiometric excess (Widlak et al., 2003).

Literature References

PubMed ID	Title	Journal	Year
15723341	Discovery, regulation, and action of the major apoptotic nucleases DFF40/CAD and endonuclease G Widlak, P, Garrard, WT	J Cell Biochem	2005
10713148	Cleavage preferences of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease) on naked DNA and chromatin substrates Widlak, P, Li, P, Wang, X, Garrard, WT	J Biol Chem	2000
10318789	Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1 Liu, X, Zou, H, Widlak, P, Garrard, W, Wang, X	J Biol Chem	1999
12748178	Subunit structures and stoichiometries of human DNA fragmentation factor proteins before and after induction of apoptosis Widlak, P, Lanuszewska, J, Cary, RB, Garrard, WT	J Biol Chem	2003
9422506	A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD Enari, M, Sakahira, H, Yokoyama, H, Okawa, K, Iwamatsu, A, Nagata, S	Nature	1998