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

Mol Cell. 2000 Mar;5(3):435-43. doi: 10.1016/s1097-2765(00)80438-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis*
  • Caenorhabditis elegans / cytology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / radiation effects
  • Caenorhabditis elegans Proteins*
  • Cell Cycle / radiation effects
  • DNA Damage*
  • DNA-Binding Proteins*
  • Dose-Response Relationship, Radiation
  • Endonucleases / genetics*
  • Germ Cells / cytology*
  • Helminth Proteins / genetics*
  • Mitosis
  • Mutation
  • Radiation Tolerance / genetics
  • Recombination, Genetic / genetics

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Helminth Proteins
  • MRT-2 protein, C elegans
  • Endonucleases