Hold on for dear life

DNA within the nuclei got minced into pieces that were multiples of 200 base pairs in length—the result of enzymes cutting between the nucleosomes. As in a dying cell, the nuclear membrane blebbed and extruded dense balls of chromatin. And the researchers found that zinc, which can stall apoptosis, prevented the nuclei from deteriorating. The results were important because they allowed researchers to create synchronized systems to study how protein-slicing enzymes such as the caspases orchestrate apoptosis, says Earn-shaw. His group was the fi rst to capitalize on this new ability (La-zebnik et al., 1994), identifying the specifi c amino acid sequence where caspases clip the DNA repair protein PARP. But if Lazebnik hadn't gone to that seminar, says Earnshaw, the researchers might still think that they had been looking at mitosis. ML S ome cells can't bear to leave home. As Steve Frisch (now at West Virginia University in Morgantown) and Hunter Francis reported in 1994, epithelial cells that lose touch with the extracellular matrix (ECM) kill themselves, a phenomenon the scientists dubbed " anoikis. " Although other researchers were skeptical at fi rst, this type of apoptosis turned out to be an important mechanism for managing cell numbers, preventing abnormal growth, and squelching cancer. Frisch and Francis weren't searching for new cell death pathways when they chanced on anoikis. The pair was scrutinizing a bizarre adenovirus protein called E1a that can restore tumor cells to normal behavior. The researchers observed that tumor cells " reverse transformed " by E1a die when they separate from the ECM. E1a also bestows some epithelial character istics on the reverse transformed cells, so Frisch and Francis decided to test whether disengagement from the ECM is fatal for normal epithelial cells. They transferred normal epithe-lial cells to culture dishes coated with a compound that prevents cellular attachment. On gels, DNA from the free-fl oating cells showed a " ladder " pattern of equal-sized snippets, a telltale sign of the DNA degradation that occurs during apoptosis (Frisch and Fran-cis, 1994). The researchers also detected breakdown products of the nuclear lamina, a sign that the nuclear envelope was disintegrating , another hallmark of apoptosis. To confi rm that separation from the ECM triggered death, the researchers raised cells on a congenial surface and then added small proteins that obstructed integrins, the membrane receptors that interact with the ECM. The cells died in droves. Frisch and …