Loss of cytidine deaminase expression as a potential attempt to counteract the process of carcinogenesis by reducing basal PARP-1 activity and increasing tau levels

Biochim Biophys Acta Mol Basis Dis. 2024 May 5;1870(5):167213. doi: 10.1016/j.bbadis.2024.167213. Online ahead of print.ABSTRACTCytidine deaminase (CDA) is a pyrimidine salvage pathway enzyme that catalyzes the hydrolytic deamination of free cytidine and deoxycytidine to uridine and deoxyuridine, respectively. Our team discovered that CDA deficiency is associated with several aspects of genetic instability, such as increased sister chromatid exchange and ultrafine anaphase bridge frequencies. Based on these results, we sought (1) to determine how CDA deficiency contributes to genetic instability, (2) to explore the possible relationships between CDA deficiency and carcinogenesis, and (3) to develop a new anticancer treatment targeting CDA-deficient tumors. This review summarizes our major findings indicating that CDA deficiency is associated with a genetic instability that does not confer an increased cancer risk. In light of our results and published data, I propose a novel hypothesis that loss of CDA, by reducing basal PARP-1 activity and increasing Tau levels, may reflect an attempt to prevent, slow or reverse the process of carcinogenesis.PMID:38714266 | DOI:10.1016/j.bbadis.2024.167213
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Source Type: research