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E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis

Ackermann, L., Schell, M., Pokrzywa, W., Kevei, E., Gartner, A., Schumacher, B. and Hoppe, T. (2016) E4 ligase–specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis. Nature structural & molecular biology, 23 (11). pp. 995-1002. ISSN 1545-9985

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To link to this item DOI: 10.1038/nsmb.3296

Abstract/Summary

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.

Item Type:Article
Refereed:Yes
Divisions:Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:67193
Publisher:Nature Publishing Group

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