title: FANCE: the link between Fanconi anaemia complex assembly and activity.
abstract: The Fanconi anaemia (FA) nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 by monoubiquitylation; this then forges an association with the BRCA1 protein at sites of DNA damage. Here we show that the recently identified FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage.
authors.affiliation: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Pace
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.forename: Wu Meng
authors.initials: WM
authors.lastname: Tan
authors.forename: Georgina
authors.initials: G
authors.lastname: Mosedale
authors.forename: Chelvin
authors.initials: C
authors.lastname: Sng
authors.forename: Maureen
authors.initials: M
authors.lastname: Hoatlin
authors.forename: Johan
authors.initials: J
authors.lastname: de Winter
authors.forename: Hans
authors.initials: H
authors.lastname: Joenje
authors.forename: Fanni
authors.initials: F
authors.lastname: Gergely
authors.forename: K J
authors.initials: KJ
authors.lastname: Patel
mesh_terms: D021581:Active Transport, Cell Nucleus; D019943:Amino Acid Substitution; D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis; D019556:COS Cells; D018797:Cell Cycle Proteins; D002460:Cell Line; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D019457:Chromosome Breakage; D004268:DNA-Binding Proteins / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism*; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052239:Fanconi Anemia Complementation Group E Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000032:analysis; D046911:Macromolecular Substances; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; C499905:FANCD2 protein, human; C499907:FANCE protein, human; C499901:FANCF protein, human; C499909:FANCG protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D052236:Fanconi Anemia Complementation Group D2 Protein; D052239:Fanconi Anemia Complementation Group E Protein; D052219:Fanconi Anemia Complementation Group F Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; C054562:yellow fluorescent protein, Bacteria