Incorporation of Nucleoside Analogs into Nuclear or Mitochondrial DNA Is Determined by the Intracellular Phosphorylation Site

摘要: Nucleoside analogs used in cancer chemotherapy and treatment of virus infections are phosphorylated cells by nucleoside nucleotide kinases to their pharmacologically active form. The incorporated into DNA cause cell death or inhibit viral replication. Cellular is replicated both the nucleus mitochondria, may interfere with replication these subcellular locations. In present study we created a model system where were phosphorylated, thereby activated, either nucleus, cytosol, mitochondria cells. was based on reconstitution deoxycytidine kinase (dCK)-deficient Chinese hamster ovary genetically engineered dCK targeted different compartments. predominantly mitochondrial DNA, whereas cytosol nuclear DNA. We further show that induced an apoptotic program. These data showed site analog phosphorylation important determinant for incorporation