PT  - JOURNAL ARTICLE
AU  - Boumard, Benjamin
AU  - Meur, Gwenn Le
AU  - Stefanutti, Marine
AU  - Maalouf, Tania
AU  - El-Hajj, Marwa
AU  - Bauer, Reinhard
AU  - Bardin, Allison J.
TI  - Cell-type-specific nucleotide sharing through gap junctions impacts sensitivity to replication stress
AID  - 10.1101/2023.08.15.553366
DP  - 2024 Jan 01
TA  - bioRxiv
PG  - 2023.08.15.553366
4099  - http://biorxiv.org/content/early/2024/09/17/2023.08.15.553366.short
4100  - http://biorxiv.org/content/early/2024/09/17/2023.08.15.553366.full
AB  - Cell proliferation underlying tissue growth and homeostasis, requires high levels of metabolites such as deoxynucleotides (dNTPs). The dNTP pool is known to be tightly cell-autonomously regulated via de novo synthesis and salvage pathways. Here, we reveal that nucleotides can also be provided to cells non-autonomously by surrounding cells within a tissue. Using Drosophila epithelial tissues as models, we find that adult intestinal stem cells are highly sensitive to nucleotide depletion whereas wing progenitor cells are not. Wing progenitor cells share nucleotides through gap junction connections, allowing buffering of replication stress induced by nucleotide pool depletion. Adult intestinal stem cells, however, lack gap junctions and cannot receive dNTPs from neighbors. Collectively, our data suggest that gap junction-dependent sharing between cells can contribute to dNTP pool homeostasis in vivo. We propose that inherent differences in cellular gap junction permeability can influence sensitivity to fluctuations of intracellular dNTP levels.One-Sentence Summary The nucleotide pool can be shared between adjacent cells through gap junctions allowing tissue-level buffering of replication stress.Competing Interest StatementThe authors have declared no competing interest.