Universität zu Köln

Ackermann, Leena ORCID: 0000-0001-6405-900X, Schell, Michael, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462, Kevei, Eva ORCID: 0000-0002-0560-9208, Gartner, Anton ORCID: 0000-0003-4639-9902, Schumacher, Bjoern and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2016). E4 ligase-specific ubiquitination hubs coordinate DNA double-strand-break repair and apoptosis. Nat. Struct. Mol. Biol., 23 (11). S. 995 - 1003. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1545-9985

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ackermann, Leena UNSPECIFIED orcid.org/0000-0001-6405-900X UNSPECIFIED Schell, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Pokrzywa, Wojciech UNSPECIFIED orcid.org/0000-0002-5110-4462 UNSPECIFIED Kevei, Eva UNSPECIFIED orcid.org/0000-0002-0560-9208 UNSPECIFIED Gartner, Anton UNSPECIFIED orcid.org/0000-0003-4639-9902 UNSPECIFIED Schumacher, Bjoern UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-257318
DOI:	10.1038/nsmb.3296
Journal or Publication Title:	Nat. Struct. Mol. Biol.
Volume:	23
Number:	11
Page Range:	S. 995 - 1003
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1545-9985
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DAMAGE-INDUCED APOPTOSIS; NEMATODE CAENORHABDITIS-ELEGANS; C. ELEGANS; SELECTIVE CHAPERONE; PROTEASOME SYSTEM; TUMOR-SUPPRESSOR; PROTEIN; CDC48/P97; P53; MULTIUBIQUITYLATION Multiple languages Biochemistry & Molecular Biology; Biophysics; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/25731