L. Fischer, H. Straube, N. Passon, H. Thoelke, C.-P. Witte, M. Herde
Demonstrated that VENOSA4, a dNTP triphosphohydrolase, converts de novo-synthesized dNTPs to deoxynucleosides (dNs) in Arabidopsis. Preventing this conversion by VEN4 mutation strongly diminished cpDNA and mtDNA amounts, which could be partially rescued by exogenous dNs. VENOSA4 ensures sufficient DNA precursors in form of dNs reach chloroplasts and mitochondria for DNA synthesis.
The replication of the three genomes in plant cells during germination is a complex process, which requires a high degree of coordination between the genome-containing compartments: the nucleus, mitochondria, and chloroplasts. The first committed step for the de novo synthesis of deoxynucleoside triphosphates (dNTPs), the building blocks for DNA replication, occurs exclusively in the cytosol. A major unresolved question is how an adequate supply of dNTPs for the organelles is achieved. Here, we show that VENOSA4 (VEN4), a dNTP triphosphohydrolase, is critical for this process in Arabidopsis thaliana. Using isotope feeding combined with mass spectrometry analysis, we demonstrate that VEN4 converts most de novo-synthesized dNTPs to deoxynucleosides (dNs). Preventing this conversion by VEN4 mutation strongly diminishes both cpDNA and mtDNA amounts, but these can be partially rescued by the application of exogenous dNs. Hence, the dNTP catabolic activity of VEN4 ensures that sufficient DNA precursors in form of dNs reach the chloroplasts and the mitochondria to be salvaged there to dNTPs for DNA synthesis. This seemingly counterintuitive coupling of de novo synthesis, dNTP hydrolysis, and salvage may provide a mechanism to control DNA precursor allocation between cellular compartments through selective transport and metabolic trapping.