Figure 8.

89-kDa PARP1 fragment serves as a PAR carrier to promote AIF-mediated cell death after caspase activation. (1) Caspase-3 activation results in the cleavage of poly(ADP-ribosyl)ated PARP1 that accumulated at DNA lesions into the 24-kDa and 89-kDa PARP1 fragments. (2) The 89-kDa PARP1 fragment with attached PAR polymers is translocated from the nucleus to the cytoplasm, whereas the 24-kDa PARP1 continuously associates with DNA lesions. (3) PAR polymers attached to the 89-kDa PARP1 fragments bind AIF, resulting in AIF release from mitochondrial membranes. (4) AIF is translocated to the nucleus where it induces large-scale DNA fragmentation by DNAase, resulting in cell death. AIF, apoptosis-inducing factor.