論文 - 詳細
| RRC ID | 51474 |
|---|---|
| 著者 | Edifizi D, Nolte H, Babu V, Castells-Roca L, Mueller MM, Brodesser S, Krüger M, Schumacher B. |
| タイトル | Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans. |
| ジャーナル | Cell Rep |
| Abstract |
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage. We derive metabolic changes indicative of a tissue maintenance program and implicate an autophagy-mediated proteostatic response. We assign central roles for the insulin-, EGF-, and AMPK-like signaling pathways in orchestrating the adaptive response to DNA damage. Our results provide insights into the DNA damage responses in the organismal context. |
| 巻・号 | 20(9) |
| ページ | 2026-2043 |
| 公開日 | 2017-8-29 |
| DOI | 10.1016/j.celrep.2017.08.028 |
| PII | S2211-1247(17)31135-X |
| PMID | 28854356 |
| PMC | PMC5583510 |
| MeSH | Active Transport, Cell Nucleus / radiation effects Aging / metabolism Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / metabolism* Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / metabolism Cell Nucleus / metabolism Cell Nucleus / radiation effects Cellular Reprogramming* / radiation effects DNA Damage* DNA Repair / radiation effects Down-Regulation / radiation effects Ion Transport / radiation effects Lipid Metabolism / radiation effects Mutation / genetics Phosphoproteins / metabolism Proteolysis / radiation effects Proteome / metabolism Proteomics Starvation / metabolism Synaptic Transmission / radiation effects Transcriptome / genetics Transcriptome / radiation effects Ultraviolet Rays Up-Regulation / radiation effects |
| IF | 8.109 |
| 引用数 | 6 |
| リソース情報 | |
| 線虫 | tm3886 |