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 show that genotoxic stress blocks cell proliferation and induces apoptosis of germ cells in the nematode C. elegans. Accumulation of recombination intermediates similarly leads to the demise of affected cells. Checkpoint-induced apoptosis is mediated by the core apoptotic machinery (CED-9/CED-4/CED-3) but is genetically distinct from somatic cell death and physiological germ 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 DNA damage-induced apoptosis and cell proliferation arrest. Our results implicate rad1 homologs in DNA damage-induced apoptosis in animals.
Gartner
A
A
Cold Spring Harbor Laboratory, New York 11724, USA.
Milstein
S
S
Ahmed
S
S
Hodgkin
J
J
Hengartner
M O
MO
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000528:radiation effects; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle / Q000528:radiation effects; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004720:Endonucleases / Q000235:genetics*; D005854:Germ Cells / Q000166:cytology*; D015801:Helminth Proteins / Q000235:genetics*; D008938:Mitosis; D009154:Mutation; D011836:Radiation Tolerance / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; C403443:MRT-2 protein, C elegans; D004720:Endonucleases