論文 - 詳細
| RRC ID | 51490 |
|---|---|
| 著者 | Wilson DM 3rd, Rieckher M, Williams AB, Schumacher B. |
| タイトル | Systematic analysis of DNA crosslink repair pathways during development and aging in Caenorhabditis elegans. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
DNA interstrand crosslinks (ICLs) are generated by endogenous sources and chemotherapeutics, and pose a threat to genome stability and cell survival. Using Caenorhabditis elegans mutants, we identify DNA repair factors that protect against the genotoxicity of ICLs generated by trioxsalen/ultraviolet A (TMP/UVA) during development and aging. Mutations in nucleotide excision repair (NER) components (e.g. XPA-1 and XPF-1) imparted extreme sensitivity to TMP/UVA relative to wild-type animals, manifested as developmental arrest, defects in adult tissue morphology and functionality, and shortened lifespan. Compensatory roles for global-genome (XPC-1) and transcription-coupled (CSB-1) NER in ICL sensing were exposed. The analysis also revealed contributions of homologous recombination (BRC-1/BRCA1), the MUS-81, EXO-1, SLX-1 and FAN-1 nucleases, and the DOG-1 (FANCJ) helicase in ICL resolution, influenced by the replicative-status of the cell/tissue. No obvious or critical role in ICL repair was seen for non-homologous end-joining (cku-80) or base excision repair (nth-1, exo-3), the Fanconi-related proteins BRC-2 (BRCA2/FANCD1) and FCD-2 (FANCD2), the WRN-1 or HIM-6 (BLM) helicases, or the GEN-1 or MRT-1 (SNM1) nucleases. Our efforts uncover replication-dependent and -independent ICL repair networks, and establish nematodes as a model for investigating the repair and consequences of DNA crosslinks in metazoan development and in adult post-mitotic and proliferative germ cells. |
| 巻・号 | 45(16) |
| ページ | 9467-9480 |
| 公開日 | 2017-9-19 |
| DOI | 10.1093/nar/gkx660 |
| PII | 4056235 |
| PMID | 28934497 |
| PMC | PMC5766164 |
| MeSH | Aging* / drug effects Aging* / physiology Aging* / radiation effects Animals Caenorhabditis elegans / drug effects Caenorhabditis elegans / growth & development Caenorhabditis elegans / physiology* Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / genetics DNA / chemistry DNA Repair* / drug effects DNA Repair* / radiation effects Female Homologous Recombination Male Mutation Trioxsalen / pharmacology Ultraviolet Rays |
| IF | 11.502 |
| 引用数 | 5 |
| 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 | X(Twitter) |
| 各媒体での言及数の合計 | 12 |
| 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 | tm1086 tm1145 tm1298 tm1354 tm1670 tm1842 tm1937 tm1981 tm2073 tm2181 tm2644 tm2842 tm2940 tm3886 tm423 tm5232 |