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

Anton Gartner, Stuart Milstein, Shawn Ahmed, Jonathan Hodgkin, Michael O. Hengartner

    Research output: Contribution to journalArticle

    367 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)435-443
    Number of pages9
    JournalMolecular Cell
    Volume5
    Issue number3
    DOIs
    Publication statusPublished - 2000

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