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Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation

Oncogene volume 23, pages 5004–5013 (2004)Cite this article

Abstract

Loss of Fanconi anemia (FA) proteins activity by recessive inherited mutations in one of the FA genes leads to a disease characterized by bone marrow failure, myeloid leukemia and DNA damage hypersensitivity. The aim of this work was to improve our understanding of the FA syndrome defining the transcription profile of the FA complementation group C (FANCC)-deficient cells in comparison to their ectopically corrected counterpart using oligonucleotide microarrays. In this way, 49 RNAs have been isolated, which showed a consistent differential pattern of expression among FANCC mutated and corrected cells. The observed specific changes in gene expression suggest that FANCC regulates specifically myeloid differentiation and unmasks a previously unsuspected anti-inflammatory role for the FA proteins. In spite of the DNA damage hypersensitivity of the syndrome, no gene coding for a protein directly involved in DNA repair/damage response was found to be deregulated in our analysis. This observation suggests that FANCC does not directly control genes involved in DNA repair at the transcriptional level, but does not exclude a regulation at the translational or post-translational level, or by protein/protein interactions. The potential role of the differentially expressed genes in FA phenotype as well as a functional- and cellular-based clustering of the identified genes are presented and discussed.

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Acknowledgements

We thank Dr C Guillouf for helpful discussion, and C Wanherdrick and R Culerrier for excellent technical assistance. This work was supported by Grant from the Association pour la Recherche contre le Cancer (ARC), Fondation de France, GEFLUC and the Ministere de la Recherche, France. R Zanier was a fellow of CNR, Italy.

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  1. UPR2169 CNRS, Institut Gustave Roussy, 39, rue Camille Desmoulins, Villejuif cedex, 94805, France

    Romina Zanier, Delphine Briot, Jean-Antoine Dugas du Villard, Alain Sarasin & Filippo Rosselli

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Correspondence to Filippo Rosselli.

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Zanier, R., Briot, D., Villard, JA. et al. Fanconi anemia C gene product regulates expression of genes involved in differentiation and inflammation. Oncogene 23, 5004–5013 (2004). https://doi.org/10.1038/sj.onc.1207677

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