Association of HMGB1/HMGB2 with chromatin Cleavage of DNA by DFF40 Cleaved fragments of DFF45 dissociate from DFF40 Cleavage of DFF45 (224) by caspase-3 Caspase 3-mediated cleavage of DFF45 (117) Translocation of caspase-3 to the nucleus Association of DFF40 with chromatin Homodimerization of DFF40 Translocation of DFF to the nucleus Association of DFF with alpha:beta importin Association of DFF40 with DFF45 PathwayStep4411 PathwayStep4410 PathwayStep4409 PathwayStep4412 PathwayStep4413 PathwayStep4414 PathwayStep4415 PathwayStep4416 PathwayStep4417 PathwayStep4418 PathwayStep4419 Activation of DNA fragmentation factor Authored: Matthews, L, 2008-01-29 12:03:24 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). Edited: Matthews, L, 2008-05-02 11:33:14 Pubmed10318789 Pubmed10713148 Pubmed12748178 Pubmed15723341 Pubmed9422506 Reactome Database ID Release 43211227 Reactome, http://www.reactome.org ReactomeREACT_13462 Reviewed: Widlak, P, 2008-05-07 23:54:18