title: Regulation of the Fanconi anemia pathway by monoubiquitination.
abstract: Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome characterized by multiple congenital anomalies, bone marrow failure, and cellular sensitivity to mitomycin C (MMC). To date, six FA genes have been cloned, and the encoded proteins function in a novel pathway. The FA pathway is required for the normal cellular response to DNA damage. Following DNA damage, the pathway is activated, leading to monoubiquitination of the FA protein, FANCD2, and its targeting to subnuclear foci. Disruption of the FA pathway results in the absence of FANCD2 nuclear foci, leading to the cellular and clinical abnormalities of FA. Here, we review the recent studies describing the regulated monoubiquitination of the FANCD2 protein and discuss the interaction of the FA pathway with other DNA damage response pathways.
authors.affiliation: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Mayer 640, 44 Binney Street, Boston, MA 02115, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Gregory
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Alan D
authors.initials: AD
authors.lastname: D'Andrea
mesh_terms: D004249:DNA Damage / Q000502:physiology; D004260:DNA Repair / Q000502:physiology*; D005199:Fanconi Anemia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D052236:Fanconi Anemia Complementation Group D2 Protein; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism*
chemical_list: C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; D009687:Nuclear Proteins; D014452:Ubiquitins