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bioRxiv · 10.64898/2026.03.04.709599

Position of de novo purine biosynthesis gene disruptions shapes purine-starvation phenotypes in Saccharomyces cerevisiae

Ozolina, Z.·Kokina, A.·Zile, A.·Pleiko, K.·Auzins, E. T.·Kristjuhan, A.·Liepins, J.
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Abstract

Purine starvation induces a quiescence-like and stress-resistant physiological state in Saccharomyces cerevisiae, but it remains unclear whether this response is uniform across all disruptions of the de novo adenine biosynthetic pathway. Here, we used a pathway-position series of adenine-biosynthesis deletion mutants to test how the location of the metabolic blockage shapes cellular adaptation to purine starvation, using nitrogen starvation as a reference condition. Across mutants, purine starvation induced a shared core response marked by reduced growth, repression of ribosome-biogenesis and rRNA-processing modules, and accumulation of cells in G1/G0 phase. However, the magnitude and composition of the response varied systematically with pathway position. Early-pathway mutants showed the strongest desiccation tolerance and stress-associated transcriptional remodelling, whereas late-pathway mutants showed weaker protection. The ade16{Delta}ade17{Delta} double mutant was a distinct outlier, with altered carbon-flux distribution and limited stress resilience, suggesting that late-pathway disruption produces a physiologically different starvation state. Transcriptome analysis showed partial overlap with nitrogen starvation, but also pathway-position-dependent regulation of metabolic, ribosome-related, mitochondrial, and stress-response modules. Together, these results indicate that purine starvation is not a single physiological condition, but a set of related starvation states shaped by the position of the metabolic block within the purine biosynthetic pathway.

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Ozolina, Z., Kokina, A., Zile, A., Pleiko, K., Auzins, E. T., Kristjuhan, A., Liepins, J.. 2026-03-05. Position of de novo purine biosynthesis gene disruptions shapes purine-starvation phenotypes in Saccharomyces cerevisiae. https://doi.org/10.64898/2026.03.04.709599

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