Changes in protein expression due to deleterious mutations in the FA/BRCA pathway |
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| Authors: | Salles Daniela Cabral Rosa Estela Caseira Pizzatti Luciana Bisch Paulo M Paixão Julio Cesar de Almeida Carlos Eduardo Bonacossa Seuánez Héctor N Cabral-Neto Januario Bispo |
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| Affiliation: | aInstituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil;bGenetics Division, Instituto Nacional de Câncer, Rio de Janeiro, Brazil;cInstituto Fernandes Figueira / FIOCRUZ, Brazil;dInstituto de Radioproteção e Dosimetria, Comissão Nacional de Energia Nuclear, Rio de Janeiro, Brazil;eDepartment of Genetics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil |
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| 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. |
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| Keywords: | DNA repair DNA Damage Checkpoint Protein expression Genome stability |
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