Abstract
We used genome-wide RNA interference (RNAi) to identify genes that affect apoptosis in the C. elegans germ line. RNAi-mediated knockdown of 21 genes caused a moderate to strong increase in germ cell death. Genetic epistasis studies with these RNAi candidates showed that a large subset (16/21) requires p53 to activate germ cell apoptosis. Apoptosis following knockdown of the genes in the p53-dependent class also depended on a functional DNA damage response pathway, suggesting that these genes might function in DNA repair or to maintain genome integrity. As apoptotic pathways are conserved, orthologues of the worm germline apoptosis genes presented here could be involved in the maintenance of genomic stability, p53 activation, and fertility in mammals.
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Abbreviations
- AO:
-
acridine orange
- DIC:
-
differential interference contrast
- DTC:
-
distal tip cell
- gf :
-
gain-of-function
- gla :
-
germline apoptosis
- lf :
-
loss-of-function
- RNAi:
-
RNA-mediated interference
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Acknowledgements
We thank the C. elegans Gene Knockout Consortium and the Caenorhabditis Genetics Center, which is supported by NIH's National Center for Research Resources, for providing cep-1(gk138), pmk-3(ok169), and bmk-1(ok391) mutant strains. We thank A Hajnal and ER Hofmann for critical reading of the manuscript, and members of the Hengartner lab for comments. This work was supported by a grant from the Swiss National Science Foundation, the Josef Steiner Foundation, the Ernst Hadorn Foundation, and NIH grant GM52240. G Lettre is supported by a fellowship from the Fonds Québécois de la Recherche sur la Nature et les Technologies.
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Lettre, G., Kritikou, E., Jaeggi, M. et al. Genome-wide RNAi identifies p53-dependent and -independent regulators of germ cell apoptosis in C. elegans. Cell Death Differ 11, 1198–1203 (2004). https://doi.org/10.1038/sj.cdd.4401488
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DOI: https://doi.org/10.1038/sj.cdd.4401488
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