title: The ubiquitin family meets the Fanconi anemia proteins.
abstract: Fanconi anaemia (FA) is a hereditary disorder characterized by bone marrow failure, developmental defects, predisposition to cancer and chromosomal abnormalities. FA is caused by biallelic mutations that inactivate genes encoding proteins involved in replication stress-associated DNA damage responses. The 20 FANC proteins identified to date constitute the FANC pathway. A key event in this pathway involves the monoubiquitination of the FANCD2-FANCI heterodimer by the collective action of at least 10 different proteins assembled in the FANC core complex. The FANC core complex-mediated monoubiquitination of FANCD2-FANCI is essential to assemble the heterodimer in subnuclear, chromatin-associated, foci and to regulate the process of DNA repair as well as the rescue of stalled replication forks. Several recent works have demonstrated that the activity of the FANC pathway is linked to several other protein post-translational modifications from the ubiquitin-like family, including SUMO and NEDD8. These modifications are related to DNA damage responses but may also affect other cellular functions potentially related to the clinical phenotypes of the syndrome. This review summarizes the interplay between the ubiquitin and ubiquitin-like proteins and the FANC proteins that constitute a major pathway for the surveillance of the genomic integrity and addresses the implications of their interactions in maintaining genome stability.
authors.affiliation: CNRS UMR 8200-Equipe Labellisée "La Ligue Contre le Cancer"-Institut Gustave Roussy, 94805 Villejuif, France; Gustave Roussy Cancer Center, 94805 Villejuif, France; Université Paris Sud, 91400 Orsay, France. Electronic address: xr212@mrc-cu.cam.ac.uk.
authors.forename: Xavier
authors.initials: X
authors.lastname: Renaudin
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors.forename: Leticia
authors.initials: L
authors.lastname: Koch Lerner
authors.affiliation: Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-900, Brazil.
authors.forename: Carlos Frederico Martins
authors.initials: CF
authors.lastname: Menck
authors.affiliation: CNRS UMR 8200-Equipe Labellisée "La Ligue Contre le Cancer"-Institut Gustave Roussy, 94805 Villejuif, France; Gustave Roussy Cancer Center, 94805 Villejuif, France; Université Paris Sud, 91400 Orsay, France. Electronic address: filippo.rosselli@gustaveroussy.fr.
authors.forename: Filippo
authors.initials: F
authors.lastname: Rosselli
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability; D006801:Humans; D000075687:NEDD8 Protein; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D058207:Sumoylation; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: D005136:Eye Proteins; D051856:Fanconi Anemia Complementation Group Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; C429294:UBL5 protein, human; D014452:Ubiquitins
keywords: DNA repair; Fanconi anemia; NEDD8; Ubiquitin