Biological Consequences of Guanine Starvation

Abstract

One of the first effects of guanine starvation is a drastic inhibition of DNA synthesis. The DNA inhibition is associated with guanine, rather than adenine, nucleotide depletion [2]. Moreover, the DNA inhibition was found to be associated with GTP, rather than dGTP, depletion [1]. This was demonstrated with the use of mouse lymphoma S49 wild-type and HGPRT-ase negative mutants: DNA synthesis inhibition by mycophenolic acid (resulting in guanine nucleotide starvation by IMP dehydrogenase inhibition) in the mutant cells was not reversed by selectively establishing normal or elevated dGTP levels with exogenous deoxyguanosine (dGuo) (see metabolic pathways in Fig. 1). The same phenomenon was observed in two other cell lines (mouse L1210 and human CCRF-CEM, wild type and HGPRT-ase negative) [3], which suggests a more general applicability of the finding that DNA synthesis inhibition by guanine starvation is independent of the total dGTP cellular pool size.