論文 - 詳細
| RRC ID | 53460 |
|---|---|
| 著者 | Franz A, Pirson PA, Pilger D, Halder S, Achuthankutty D, Kashkar H, Ramadan K, Hoppe T. |
| タイトル | Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. |
| ジャーナル | Nat Commun |
| Abstract |
The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin-directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin-associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN-3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC-48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging. |
| 巻・号 | 7 |
| ページ | 10612 |
| 公開日 | 2016-2-4 |
| DOI | 10.1038/ncomms10612 |
| PII | ncomms10612 |
| PMID | 26842564 |
| PMC | PMC4743000 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Adenosine Triphosphatases / genetics* Adenosine Triphosphatases / metabolism Animals Apoptosis Regulatory Proteins Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Carrier Proteins / genetics* Carrier Proteins / metabolism Cell Cycle Proteins / genetics* Cell Cycle Proteins / metabolism Cell Line, Tumor Chromatin / metabolism* Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA Replication / genetics* Embryo, Nonmammalian HEK293 Cells Humans Immunoprecipitation Ligases / metabolism* Microscopy Time-Lapse Imaging Valosin Containing Protein |
| IF | 12.121 |
| 引用数 | 15 |
| 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 | 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 | tm544 tm659 tm6658 tm6659 |