title: Changes in protein expression due to deleterious mutations in the FA/BRCA pathway.
abstract: Inherited deleterious mutations in one of the Fanconi anemia genes lead to a disease, characterized by bone marrow failure, myeloid leukemia, and hypersensitivity to DNA damage. We identified proteins likely associated to the molecular signaling pathways involved in DNA repair of interstrand cross-link lesions and in mechanisms of genomic stability mediated by FA/BRCA pathways. We compared protein maps resolved by bidimensional electrophoresis and analyzed differentially expressed proteins, by mass spectrometry, between FA complementation group C (FANCC)-deficient cells, and their ectopically corrected counterpart in physiological conditions or after treatment with MMC. We found six differentially expressed proteins; among them, the checkpoint mediator protein MDC1 whose expression was disrupted in FANCC-/- cells. The potential role of differentially expressed proteins in FA phenotype is discussed.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salles
authors.forename: Rosa Estela Caseira
authors.initials: RE
authors.lastname: Cabral
authors.forename: Luciana
authors.initials: L
authors.lastname: Pizzatti
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Bisch
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Paixão
authors.forename: Carlos Eduardo Bonacossa
authors.initials: CE
authors.lastname: de Almeida
authors.forename: Héctor N
authors.initials: HN
authors.lastname: Seuánez
authors.forename: Januario Bispo
authors.initials: JB
authors.lastname: Cabral-Neto
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000235:genetics*; D018797:Cell Cycle Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D005199:Fanconi Anemia / Q000235:genetics*; D052218:Fanconi Anemia Complementation Group C Protein / Q000235:genetics*; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C497651:FANCC protein, human; D052218:Fanconi Anemia Complementation Group C Protein; D051856:Fanconi Anemia Complementation Group Proteins; C413163:MDC1 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators