title: DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA damage.
abstract: Ubiquitin-binding domains (UBDs) are crucial for recruiting many proteins to sites of DNA damage. Here we characterize C1orf124 (Spartan; referred to as DVC1), which has an UBZ4-type UBD found predominantly in DNA repair proteins. DVC1 associates with DNA replication factories and localizes to sites of DNA damage in human cells, in a manner that requires the ability of the DVC1 UBZ domain to bind to ubiquitin polymers in vitro and a conserved PCNA-interacting motif. DVC1 interacts with the p97 protein 'segregase'. We show that DVC1 recruits p97 to sites of DNA damage, where we propose that p97 facilitates the extraction of the translesion synthesis (TLS) polymerase (Pol) η during DNA repair to prevent excessive TLS and limit the incidence of mutations induced by DNA damage. We introduce DVC1 as a regulator of cellular responses to DNA damage that prevents mutations when DNA damage occurs.
authors.affiliation: Medical Research Council Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dundee, Scotland, UK.
authors.forename: Emily J
authors.initials: EJ
authors.lastname: Davis
authors.forename: Christophe
authors.initials: C
authors.lastname: Lachaud
authors.forename: Paul
authors.initials: P
authors.lastname: Appleton
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Macartney
authors.forename: Inke
authors.initials: I
authors.lastname: Näthke
authors.forename: John
authors.initials: J
authors.lastname: Rouse
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism*; D000074405:Valosin Containing Protein; D000099270:Y-Family DNA Polymerases
chemical_list: D000251:Adenosine Triphosphatases; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D025801:Ubiquitin; D000074405:Valosin Containing Protein; C574636:SPRTN protein, human; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases