Use of Drosophila deoxynucleoside kinase to study mechanism of toxicity and mutagenicity of deoxycytidine analogs in Escherichia coli.

ABSTRACT: Most bacteria, including Escherichia coli, lack an enzyme that can phosphorylate deoxycytidine and its analogs. Consequently, most studies of toxicity and mutagenicity of cytosine analogs use ribonucleosides such as 5-azacytidine (AzaC) and zebularine (Zeb) instead of their deoxynucleoside forms, 5-aza-2'-deoxycytidine (AzadC) and 2'-deoxy-zebularine (dZeb). The former analogs are incorporated into both RNA and DNA creating complex physiological responses in cells. To circumvent this problem, we introduced into E. coli the Drosophila deoxynucleoside kinase (Dm-dNK), which has a relaxed substrate specificity, and tested these cells for sensitivity to AzadC and dZeb. We find that Dm-dNK expression increases substantially sensitivity of cells to these analogs and dZeb is very mutagenic in cel

SUBMITTER: Betham B 

PROVIDER: S-EPMC2819640 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature