Research output: Contribution to journal › Article
Programmed cell death (or apoptosis) is an evolutionarily conserved, genetically controlled suicide mechanism for cells that, when deregulated, can lead to developmental defects, cancers, and degenerative diseases [1, 2]. In C. elegans, DNA damage induces germ cell death by signaling through cep-1/p53, ultimately leading to the activation of CED-3/caspase [3-13]. It has been hypothesized that the major regulatory events controlling cell death occur by cell-autonomous mechanisms, that is, within the dying cell. In support of this, genetic studies in C. elegans have shown that the core apoptosis pathway genes ced-4l APAF-1 and ced-3/caspase are required in cells fated to die . However, it is not known whether the upstream signals that activate apoptosis function in a cell-autonomous manner. Here we show that kri-1, an ortholog of KRIT1/CCM1, which is mutated in the human neurovascular disease cerebral cavernous malformation [14, 15], is required to activate DNA damage-dependent cell death independently of cep-1/p53. Interestingly, we find that kri-1 regulates cell death in a cell-nonautonomous manner, revealing a novel regulatory role for nondying cells in eliciting cell death in response to DNA damage.