Identification of the nuclear factor HMG2 as an activator for DFF nuclease activity.

DNA fragmentation during apoptosis is mediated by a heterodimeric protein complex, DFF45/ICAD and DFF40/CAD/CPAN. Purified DFF40 alone possesses intrinsic nuclease activity that is inhibited by its association with DFF45. The proteolytic cleavage of DFF45 by caspase-3 frees the DFF40 subunit to function as a nuclease. In the course of identifying factors that stimulate DFF activity, we have isolated a nuclear factor and identified it as the high mobility group protein 2 (HMG2). We found that bacterially expressed HMG2 is able to enhance the nuclease activity of DFF. As HMG2 has DNA bending activity (6), our data suggest that HMG proteins may augment DNA fragmentation during apoptosis through changes in chromosome structure.