RRC ID 46005
著者 Adamo A, Woglar A, Silva N, Penkner A, Jantsch V, La Volpe A.
タイトル Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in Caenorhabditis elegans.
ジャーナル Proc Natl Acad Sci U S A
Abstract Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation.
巻・号 109(9)
ページ 3440-5
公開日 2012-2-28
DOI 10.1073/pnas.1107390109
PII 1107390109
PMID 22331911
PMC PMC3295272
MeSH Animals Apoptosis / genetics* Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / physiology DNA Repair Extrachromosomal Inheritance Gene Dosage Germ Cells / pathology Germ-Line Mutation Meiosis / genetics Mutagenesis, Insertional Plasmids / genetics RNA Interference* RNA, Double-Stranded / genetics Rad51 Recombinase / physiology Sirtuins / physiology Transgenes Tumor Suppressor Protein p53 / physiology
IF 9.412
引用数 8
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm1298