Cancer: the two faces of Dicer

Apoptosis is a highly coordinated, multistep process that is often deregulated in diseases such as cancer and autoimmune disorders. It is associated with chromosomal fragmentation by deoxyribonucleases (DNases). Although many DNases have been characterized, Nakagawa et al. have discovered that Dicer, a highly conserved ribonuclease (RNase) that is known to produce small gene-silencing RNAs, also functions in chromosomal fragmentation. Researchers demonstrated that Dicer (dcr-1) gene inactivation in C. elegans blocks chromosomal fragmentation. The apoptosis executioner enzyme CED-3 caspase cleaves DCR-1 to generate a DCR-1 fragment with DNase activity that destroys its RNase function. Overexpression of the DCR1 DNase fragment induces DNA fragmentation. This discovery shows the conversion potential of an RNase to a DNase, and elucidates an important regulatory mechanism in apoptosis, which is relevant to many human diseases.