title: Loss of ubiquitin E2 Ube2w rescues hypersensitivity of Rnf4 mutant cells to DNA damage.
abstract: SUMO and ubiquitin play important roles in the response of cells to DNA damage. These pathways are linked by the SUMO Targeted ubiquitin Ligase Rnf4 that catalyses transfer of ubiquitin from a ubiquitin loaded E2 conjugating enzyme to a polySUMO modified substrate. Rnf4 can functionally interact with multiple E2s, including Ube2w, in vitro. Chicken cells lacking Rnf4 are hypersensitive to hyroxyurea, DNA alkylating drugs and DNA crosslinking agents, but this sensitivity is suppressed by simultaneous depletion of Ube2w. Cells depleted of Ube2w alone are not hypersensitive to the same DNA damaging agents. Similar results were also obtained in human cells. These data indicate that Ube2w does not have an essential role in the DNA damage response, but is deleterious in the absence of Rnf4. Thus, although Rnf4 and Ube2w functionally interact in vitro, our genetic experiments indicate that in response to DNA damage Ube2w and Rnf4 function in distinct pathways.
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, DD1 5EH, UK.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Maure
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, DD1 5EH, UK.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Moser
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, DD1 5EH, UK.
authors.forename: Ellis G
authors.initials: EG
authors.lastname: Jaffray
authors.affiliation: MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee, DD1 5EH, UK.
authors.forename: Arno
authors.initials: A
authors.lastname: F Alpi
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, DD1 5EH, UK.
authors.forename: Ronald T
authors.initials: RT
authors.lastname: Hay
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002645:Chickens; D004249:DNA Damage; D006801:Humans; D009687:Nuclear Proteins / Q000172:deficiency*; D014157:Transcription Factors / Q000172:deficiency*; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; C114070:RNF4 protein, human; D014157:Transcription Factors; C510626:UBE2W protein, human; D044763:Ubiquitin-Conjugating Enzymes