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Dr. Mounira AMOR-GUERET / Cytidine deaminase deficiency: from genetic instability to cancer in the general population
vendredi 18 mai - 11:00 à 12:30
Dr. Mounira AMOR-GUERET, UMR3348 Stress génotoxique et cancer, équipe « Instabilité génétique et cancérogenèse« , Institut Curie
The supply of deoxyribonucleotides (dNTPs) and the regulation of their pools are of great importance for successful DNA replication and repair, and thus for preventing cancer. We reported that a pyrimidine pool disequilibrium resulting from cytidine deaminase (CDA) deficiency generates a genetic instability that might potentially promote cancer development. CDA is an enzyme of the pyrimidine salvage pathway catalyzing the hydrolytic deamination of cytidine and deoxycytidine to uridine and deoxyuridine (dU), respectively. We deciphered part of the mechanism at the origin of the genetic instability in CDA-deficient cells. We also found that CDA expression is downregulated in about 60% of human tumor cell lines and primary tumors, mostly due to DNA methylation, and that CDA deficiency may turn out to be a new predictive marker of susceptibility to anti-tumor drugs.