C. elegans SIR-2.1 translocation is linked to a proapoptotic pathway parallel to cep-1/p53 during DNA damage-induced apoptosis

Sebastian Greiss, Julie Hall, Shawn Ahmed, Anton Gartner (Lead / Corresponding author)

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    Abstract

    Caenorhabditis elegans SIR-2.1, a member of the sirtuin family related to Saccharomyces cerevisiae Sir2p, has previously been implicated in aging. The mammalian homolog SIRT1 plays important roles in multiple cellular processes including transcriptional repression and stress response. We show that sir-2.1 is essential for the execution of apoptosis in response to DNA damage, and that sir-2.1 genetically acts in parallel to the worm p53-like gene cep-1. This novel cep-1-independent proapoptotic pathway does not require the daf-16 FOXO transcription factor. Cytological analysis of SIR-2.1 suggests a novel mechanism of apoptosis induction. During apoptosis SIR-2.1 changes its subcellular localization from the nucleus to the cytoplasm and transiently colocalizes with the C. elegans Apaf-1 homolog CED-4 at the nuclear periphery. SIR-2.1 translocation is an early event in germ cell apoptosis and is independent of apoptosis execution and cep- 1, raising the possibility that SIR-2.1 translocation is linked to the induction of DNA damage- induced apoptosis.

    Original languageEnglish
    Pages (from-to)2831-2842
    Number of pages12
    JournalGenes & Development
    Volume22
    Issue number20
    DOIs
    Publication statusPublished - 15 Oct 2008

    Keywords

    • sir-2.1
    • SIR2
    • sirtuin
    • C. elegans
    • DNA damage response
    • apoptosis
    • PROGRAMMED CELL-DEATH
    • CAENORHABDITIS-ELEGANS
    • LIFE-SPAN
    • SACCHAROMYCES-CEREVISIAE
    • CHECKPOINT PROTEIN
    • SIRT1 DEACETYLASE
    • TUMOR-SUPPRESSOR
    • STRAND BREAKS
    • GERM-LINE
    • P53

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