Common precursor pathways of Herpes DNA and of repair synthesis in ultraviolet irradiated cells

Abstract

DEOXYRIBONUCLEOTIDE precursors of DNA synthesis may be supplied by two alternative pathways in mammalian cells¹: (1) endogenous synthesis by reduction of the corresponding ribonucleotides at the diphosphate level, except thymidine nucleotides which are produced by deamination and methylation of cytidine deoxynucleotides at the monophosphate level; (2) exogenous salvage synthesis by stepwise phosphorylation of pre-existing deoxyribonucleosides. The first step leading to monophosphates is catalysed by purine² and pyrimidine^3,4 deoxyribonucleoside kinases. In cells infected with Herpes simplex type I (HSV) there is an induction of both thymidine kinase (TK)⁵ and deoxycytidine kinase activity⁶. These two activities seem to be a property of the same virus-specified enzyme⁷, whose role remains unclear. It seems to be important for viral DNA synthesis in resting cells⁸ in which the endogenous metabolism of DNA is low whereas the degradative phosphatase activity is high⁹. On the other hand viral TK activity increased faster during the exponential phase of viral DNA synthesis in cells irradiated with ultraviolet light before infection than in non-irradiated cells¹⁰. This suggested that viral TK may have a more important role in the synthesis of HSV DNA in ultraviolet-irradiated than in non-irradiated cells. I present here results showing that the exogenous pathways are preferentially used for both HSV replication and for DNA repair synthesis in ultraviolet-irradiated cells.