Reference - Detail
| RRC ID | 53334 |
|---|---|
| Author | Ackermann L, Schell M, Pokrzywa W, Kevei É, Gartner A, Schumacher B, Hoppe T. |
| Title | E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis. |
| Journal | Nat Struct Mol Biol |
| Abstract |
Multiple protein ubiquitination events at DNA double-strand breaks (DSBs) regulate damage recognition, signaling and repair. It has remained poorly understood how the repair process of DSBs is coordinated with the apoptotic response. Here, we identified the E4 ubiquitin ligase UFD-2 as a mediator of DNA-damage-induced apoptosis in a genetic screen in Caenorhabditis elegans. We found that, after initiation of homologous recombination by RAD-51, UFD-2 forms foci that contain substrate-processivity factors including the ubiquitin-selective segregase CDC-48 (p97), the deubiquitination enzyme ATX-3 (Ataxin-3) and the proteasome. In the absence of UFD-2, RAD-51 foci persist, and DNA damage-induced apoptosis is prevented. In contrast, UFD-2 foci are retained until recombination intermediates are removed by the Holliday-junction-processing enzymes GEN-1, MUS-81 or XPF-1. Formation of UFD-2 foci also requires proapoptotic CEP-1 (p53) signaling. Our findings establish a central role of UFD-2 in the coordination between the DNA-repair process and the apoptotic response. |
| Volume | 23(11) |
| Pages | 995-1002 |
| Published | 2016-11-1 |
| DOI | 10.1038/nsmb.3296 |
| PMID | 27669035 |
| PMC | PMC5349472 |
| MeSH | Animals Apoptosis* Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* DNA Breaks, Double-Stranded* DNA Damage DNA Repair* Gene Deletion Rad51 Recombinase / metabolism Ubiquitin-Protein Ligase Complexes / genetics Ubiquitin-Protein Ligase Complexes / metabolism* Ubiquitination* |
| IF | 11.98 |
| Times Cited | 12 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 10 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1937 tm1380 tm2842 tm2940 tm2371 tm536 |