Deoxyguanosine reverses inhibition by hydroxyurea of repair of UV-irradiated adenovirus 5

Abstract

Hydroxyurea, an inhibitor of ribonucleotide reductase, blocks the repair by normal human fibroblasts of ultraviolet light-damaged adenovirus 5. A mixture of all four DNA deoxynucleosides present with hydroxyurea reversed the inhibition, an effect consistent with the target of hydroxyurea being ribonucleotide reductase. Single deoxynucleosides were differentially effective in reversing the inhibition: deoxyguanosine reversed 100% of the HU block, deoxyadenosine 70%, deoxythymidine 55%, but deoxycytidine only 3%. The results are interpreted in the context of the known pattern of stimulation and inhibition of mammalian ribonucleotide reductase by dNTP effectors. We suggest that biological data may be important to assessing the availability of substrate for the ribonucleotide reductase molecules that provide dNTPs for DNA repair.