title: The nuclear accumulation of the Fanconi anemia protein FANCE depends on FANCC.
abstract: The Fanconi anemia (FA) protein FANCE is an essential component of the nuclear FA core complex, which is required for monoubiquitination of the downstream target FANCD2, an important step in the FA pathway of DNA cross-link repair. FANCE is predominantly localized in the nucleus and acts as a molecular bridge between the FA core complex and FANCD2, through direct binding of both FANCC and FANCD2. At present, it is poorly understood how the nuclear accumulation of FANCE is regulated and therefore we investigated the nuclear localization of this FA protein. We found that FANCE has a strong tendency to localize in the nucleus, since the addition of a nuclear export signal does not interfere with the nuclear localization of FANCE. We also demonstrate that the nuclear accumulation of FANCE does not rely solely on its nuclear localization signal motifs, but also on FANCC. The other FA proteins are not involved in the nuclear accumulation of FANCE, indicating a tight relationship between FANCC and FANCE, as suggested from their direct interaction. Finally, we show that the region of FANCE interacting with FANCC appears to be different from the region involved in binding FANCD2. This strengthens the idea that FANCE recruits FANCD2 to the core complex, without interfering with the binding of FANCC.
authors.affiliation: Department of Clinical Genetics and Human Genetics, VU University Medical Center, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: France
authors.initials: F
authors.lastname: Léveillé
authors.forename: Miriam
authors.initials: M
authors.lastname: Ferrer
authors.forename: Annette L
authors.initials: AL
authors.lastname: Medhurst
authors.forename: El Houari
authors.initials: el H
authors.lastname: Laghmani
authors.forename: Martin A
authors.initials: MA
authors.lastname: Rooimans
authors.forename: Patrick
authors.initials: P
authors.lastname: Bier
authors.forename: Jurgen
authors.initials: J
authors.lastname: Steltenpool
authors.forename: Tom A
authors.initials: TA
authors.lastname: Titus
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.forename: Maureen E
authors.initials: ME
authors.lastname: Hoatlin
authors.forename: Hans
authors.initials: H
authors.lastname: Joenje
authors.forename: Johan P
authors.initials: JP
authors.lastname: de Winter
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D052218:Fanconi Anemia Complementation Group C Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D052239:Fanconi Anemia Complementation Group E Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D016297:Mutagenesis, Site-Directed; D049790:Nuclear Export Signals / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: C497651:FANCC protein, human; C499907:FANCE protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D052239:Fanconi Anemia Complementation Group E Protein; D049790:Nuclear Export Signals; D011994:Recombinant Proteins