Figure 1
From: New insights into the synergism of nucleoside analogs with radiotherapy
Activation of dCK after radiation contributes to enhanced therapeutic effects of nucleoside analogs. Treatment with ionizing radiation causes double strand breaks in DNA and activates the serine/threonine kinase Ataxia-telangiectasia mutated (ATM) which, in turn, phosphorylates deoxycytidine kinase, leading to a synergistic effect with nucleoside analogs. For example, gemcitabine enters the cell via the hENT1 transporter and is rapidly phosphorylated to the monophosphate form by active, serine 74 phosphorylated dCK prior to incorporation into DNA.