title: Recent discoveries in the molecular pathogenesis of the inherited bone marrow failure syndrome Fanconi anemia.
abstract: Fanconi anemia (FA) is a rare autosomal and X-linked genetic disease characterized by congenital abnormalities, progressive bone marrow failure (BMF), and increased cancer risk during early adulthood. The median lifespan for FA patients is approximately 33years. The proteins encoded by the FA genes function together in the FA-BRCA pathway to repair DNA damage and to maintain genome stability. Within the past two years, five new FA genes have been identified-RAD51/FANCR, BRCA1/FANCS, UBE2T/FANCT, XRCC2/FANCU, and REV7/FANCV-bringing the total number of disease-causing genes to 21. This review summarizes the discovery of these new FA genes and describes how these proteins integrate into the FA-BRCA pathway to maintain genome stability and critically prevent early-onset BMF and cancer.
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Road, Kingston, RI 02881, United States. Electronic address: nicholasmamrak@my.uri.edu.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Mamrak
authors.affiliation: Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center, Boston, MA 02215, United States. Electronic address: akiko.shimamura@childrens.harvard.edu.
authors.forename: Akiko
authors.initials: A
authors.lastname: Shimamura
authors.affiliation: Department of Cell and Molecular Biology, University of Rhode Island, 120 Flagg Road, Kingston, RI 02881, United States. Electronic address: nhowlett@uri.edu.
authors.forename: Niall G
authors.initials: NG
authors.lastname: Howlett
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005199:Fanconi Anemia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics / Q000378:metabolism; D042822:Genomic Instability; D059765:Homologous Recombination; D006801:Humans; D064246:Mad2 Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; D051856:Fanconi Anemia Complementation Group Proteins; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D025801:Ubiquitin; C113187:XRCC2 protein, human; C513404:UBE2T protein, human; D044763:Ubiquitin-Conjugating Enzymes; D051135:Rad51 Recombinase
keywords: DNA repair; Fanconi anemia; Genome instability; Homologous recombination; Ubiquitin