One characteristic of apoptotic cell death is the extensive fragmentation of nuclear DNA, which depends on a DNase called CAD. According to a report in Current Biology, however, this might not be the whole story.

The twist in the tale began with a screen for proteins that contain the caspase-recruitment domain (CARD), which mediates protein–protein interactions in pro-apoptotic signalling pathways. Jürg Tschopp and colleagues identified a new protein that contains two amino-terminal CARD domains and a predicted helicase domain, hence its name — Helicard.

Transient transfection of 293T cells with Helicard led to the expression of full-length Helicard, but also to the appearance of a 45-kDa fragment. Then, when FasL was used to induce apoptosis in these cells, two further fragments were generated. The authors calculated that these processing events occurred in the region between the CARD and helicase domains.

Confocal microscopy showed that, on cleavage of Helicard in apoptotic cells, the CARD-containing fragment remains in the cytoplasm, whereas the helicase domain translocates to the nucleus. Tschopp and colleagues then showed that supernatants that contain recombinant Helicard sensitized non-apoptotic extracts to DNA fragmentation.

Although Helicard has no intrinsic DNase activity, the authors speculate that it might facilitate CAD-mediated cleavage. It probably does this through its helicase activity, which opens up the DNA to allow easier access for CAD — a clever twist indeed.