| DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes ubiquitin-dependent responses to replication blocks. | |
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MedLine Citation:
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PMID: 23042605 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Ubiquitin-mediated processes orchestrate critical DNA-damage signaling and repair pathways. We identify human DVC1 (C1orf124; Spartan) as a cell cycle-regulated anaphase-promoting complex (APC) substrate that accumulates at stalled replication forks. DVC1 recruitment to sites of replication stress requires its ubiquitin-binding UBZ domain and PCNA-binding PIP box motif but is independent of RAD18-mediated PCNA monoubiquitylation. Via a conserved SHP box, DVC1 recruits the ubiquitin-selective chaperone p97 to blocked replication forks, which may facilitate p97-dependent removal of translesion synthesis (TLS) DNA polymerase η (Pol η) from monoubiquitylated PCNA. DVC1 knockdown enhances UV light-induced mutagenesis, and depletion of human DVC1 or the Caenorhabditis elegans ortholog DVC-1 causes hypersensitivity to replication stress-inducing agents. Our findings establish DVC1 as a DNA damage-targeting p97 adaptor that protects cells from deleterious consequences of replication blocks and suggest an important role of p97 in ubiquitin-dependent regulation of TLS. |
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Authors:
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Anna Mosbech; Ian Gibbs-Seymour; Konstantinos Kagias; Tina Thorslund; Petra Beli; Lou Povlsen; Sofie Vincents Nielsen; Stine Smedegaard; Garry Sedgwick; Claudia Lukas; Rasmus Hartmann-Petersen; Jiri Lukas; Chunaram Choudhary; Roger Pocock; Simon Bekker-Jensen; Niels Mailand |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-07 |
Journal Detail:
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Title: Nature structural & molecular biology Volume: - ISSN: 1545-9985 ISO Abbreviation: Nat. Struct. Mol. Biol. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101186374 Medline TA: Nat Struct Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Ubiquitin Signaling Group, Department of Disease Biology, Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. [2]. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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