論文 - 詳細
| RRC ID | 46461 |
|---|---|
| 著者 | Vermezovic J, Stergiou L, Hengartner MO, d'Adda di Fagagna F. |
| タイトル | Differential regulation of DNA damage response activation between somatic and germline cells in Caenorhabditis elegans. |
| ジャーナル | Cell Death Differ |
| Abstract |
The germline of Caenorhabditis elegans is a well-established model for DNA damage response (DDR) studies. However, the molecular basis of the observed cell death resistance in the soma of these animals remains unknown. We established a set of techniques to study ionizing radiation-induced DNA damage generation and DDR activation in a whole intact worm. Our single-cell analyses reveal that, although germline and somatic cells show similar levels of inflicted DNA damage, somatic cells, differently from germline cells, do not activate the crucial apical DDR kinase ataxia-telengiectasia mutated (ATM). We also show that DDR signaling proteins are undetectable in all somatic cells and this is due to transcriptional repression. However, DNA repair genes are expressed and somatic cells retain the ability to efficiently repair DNA damage. Finally, we demonstrate that germline cells, when induced to transdifferentiate into somatic cells within the gonad, lose the ability to activate ATM. Overall, these observations provide a molecular mechanism for the known, but hitherto unexplained, resistance to DNA damage-induced cell death in C. elegans somatic cells. We propose that the observed lack of signaling and cell death but retention of DNA repair functions in the soma is a Caenorhabditis-specific evolutionary-selected strategy to cope with its lack of adult somatic stem cell pools and regenerative capacity. |
| 巻・号 | 19(11) |
| ページ | 1847-55 |
| 公開日 | 2012-11-1 |
| DOI | 10.1038/cdd.2012.69 |
| PII | cdd201269 |
| PMID | 22705849 |
| PMC | PMC3469062 |
| MeSH | Animals Apoptosis Ataxia Telangiectasia Mutated Proteins Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism DNA Damage DNA Repair* DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Germ Cells / metabolism* Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Radiation, Ionizing Signal Transduction Single-Cell Analysis Tumor Suppressor Proteins / genetics Tumor Suppressor Proteins / metabolism |
| IF | 10.717 |
| 引用数 | 34 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1524 tm853 tm1724 |