A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans

To maintain genomic stability following DNA damage, multicellular organisms activate checkpoints that induce cell cycle arrest or apoptosis. Here we s how that genotoxic stress blocks cell proliferation and induces apoptosis o f germ cells in the nematode C. elegans. Accumulation of recombination inte rmediates similarly leads to the demise of affected cells. Checkpoint-induc ed apoptosis is mediated by the core apoptotic machinery (CED-S/CED-4/CED-3 ) but is genetically distinct from somatic cell death and physiological ger m cell death. Mutations in three genes-mrt-2, which encodes the C. elegans homolog of the S. pombe rad1 checkpoint gene, rad-5, and him-7-block both D NA damage-induced apoptosis and cell proliferation arrest. Our results impl icate rad1 homologs in DNA damage-induced apoptosis in animals.