RRC ID 4234
Author Greiss S, Hall J, Ahmed S, Gartner A.
Title C. elegans SIR-2.1 translocation is linked to a proapoptotic pathway parallel to cep-1/p53 during DNA damage-induced apoptosis.
Journal Genes Dev.
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.
Volume 22(20)
Pages 2831-42
Published 2008-10-15
DOI 10.1101/gad.482608
PII 22/20/2831
PMID 18923081
PMC PMC2569882
MeSH Animals Apoptosis / physiology* Blotting, Western Caenorhabditis elegans / genetics* Caenorhabditis elegans / growth & development Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Calcium-Binding Proteins / genetics Calcium-Binding Proteins / metabolism Cell Differentiation Cell Nucleus / metabolism Cytoplasm / metabolism DNA Damage* DNA Repair Forkhead Transcription Factors Germ Cells / cytology Germ Cells / metabolism Protein Transport* Sirtuins / genetics* Sirtuins / metabolism Subcellular Fractions Transcription Factors / genetics Transcription Factors / metabolism Tumor Suppressor Protein p53 / genetics* Tumor Suppressor Protein p53 / metabolism
IF 9.462
Times Cited 45
C.elegans tm853