Unlike necrosis, apoptosis (programmed cell death) is generally beneficial to an organism and loss of apoptotic pathways can lead to uncontrolled cell proliferation. Apoptosis takes place, for example, when a cell is irreparably damaged or infected by a virus and the signal for apoptosis can come from the cell itself, from surrounding tissue, or from immune cells. Although a variety of signals and pathways can trigger apoptosis, it is ultimately the action of caspases that degrades cellular organelles and proteins. Chromosome fragmentation is a hallmark of apoptosis and, in mammals, caspases activate apoptotic chromosome fragmentation by cleaving and inactivating an apoptotic nuclease inhibitor.
Working with C. elegans, a team led by researchers at the University of Colorado at Boulder have now shown that the Dicer ribonuclease (DCR-1), instead of being inactivated by caspases, undergoes a change of function. DCR-1 normally processes small RNAs but cleavage by the CED-3 caspase produces a C-terminal fragment which shows deoxyribonuclease activity and produces 3′ hydroxyl DNA breaks on chromosomes and promotes apoptosis. Although there are many enzymes that cleave either RNA or DNA, this is the first demonstration that proteolysis of a ribonuclease can generate a deoxyribonuclease.
The researchers are now investigating whether the function of DCR-1 can be altered in the same way in human cells – if so, the authors hope that their work may lead to new ways to treat diseases caused by abnormal apoptosis such as cancer and autoimmune diseases.
The study is published in the journal Science.