Nucleotide synthesis

Biological process · 6 studies in the Atlas

De novo purine and pyrimidine production. mTORC1 matches supply to demand here, which is why proliferating cells are so dependent on it.

Making DNA and RNA building blocks. Building the raw materials (DNA/RNA letters) from scratch. mTORC1 ramps this up to match how fast a cell is dividing, which is a big part of why rapidly growing cells depend on mTOR so heavily.

S6K1 phosphorylates CAD for pyrimidines; ATF4–MTHFD2 supports purines. A growth output that is often forgotten next to translation.

TL;DR. Nucleotide synthesis appears in 6 curated studies in Oliver's mTOR Atlas: 6 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 3 interactions in the curated pathway model.

In the pathway model

3 interactions in the curated mTOR pathway model. Each row is a claim with the evidence behind it; the evidence code is the kind of study, not its quality.

Interaction	Mechanism	Evidence	Studies
mTORC1 activates Nucleotide synthesis mechanism: signal-relay · this link in full · on the map table	mTORC1 turns on the machinery for building DNA/RNA building blocks, so a growing cell can actually copy its DNA.mTORC1 couples nucleotide supply to demand - it turns on purine synthesis through the mitochondrial tetrahydrofolate cycle so a dividing cell can actually copy its DNA. Holds under: Cancer cell and mammalian cell studies, including xenograft tumours (VAL2017, BEN2016, ALI2022). The evidence comes mostly from dividing or tumour cells; whether non-dividing tissues use the same route is not shown. plausible in people, not shown directly · settled in the literature	M	VAL2017, BEN2016, ALI2022
S6K1 activates Nucleotide synthesis mechanism: phosphorylation · this link in full · on the map table	S6K1 switches on an enzyme that starts building the raw materials for DNA – a direct line from growth signal to DNA parts.S6K1 phosphorylates CAD, the enzyme that starts de novo pyrimidine synthesis - a direct line from growth signal to DNA building blocks. Holds under: Mammalian cell studies including xenograft tumours (BEN2013, ROB2013, ALI2022). The evidence comes from cultured and tumour cells; whether non-dividing tissues use the same route is not shown. plausible in people, not shown directly · settled in the literature	M	BEN2013, ROB2013, ALI2022
ERK / RSK (MAPK) activates Nucleotide synthesis mechanism: phosphorylation · this link in full · on the map table	ERK2 switches on an enzyme that makes purines.ERK2 directly phosphorylates the purine-making enzyme PFAS within minutes, speeding de novo purine synthesis. This growth signal for DNA and RNA building blocks runs in parallel to mTORC1's own routes. Holds under: Human cancer cell lines and xenograft tumours; ERK2, not ERK1; post-translational and parallel to mTORC1. Single study. plausible in people, not shown directly · emerging, few independent studies	M	ALI2020

Evidence at a glance

Evidence	What it means	Studies
M	Molecular — cells, biochemistry, structure	6

No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.

Studies

Year	Evidence	Study
2022	M	The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis ALI2022 Building a nucleotide needs a carbon donor, and cells get it from bicarbonate dissolved in their surroundings. This study shows mTORC1 does not just switch on the nucleotide enzymes - it also arranges the delivery of the raw material. Through S6K and the translation factor eIF4B, mTORC1 selectively increases translation of the mRNA for SLC4A7, a sodium-bicarbonate cotransporter, so more bicarbonate is pulled into the cell. Removing SLC4A7 from cells with hyperactive mTORC1 cut flux through both de novo purine and pyrimidine synthesis and slowed cell and tumor growth, without changing intracellular pH - so the transporter matters as a supply line, not as a pH regulator. A fourth distinct route by which mTORC1 feeds nucleotide synthesis, alongside CAD (BEN2013), the mitochondrial folate cycle (BEN2016) and demand coupling (VAL2017).
2020	M	ERK2 phosphorylates PFAS to mediate posttranslational control of de novo purine synthesis ALI2020 The Atlas records several routes by which mTORC1 drives purine synthesis. This study shows mTORC1 is not the only growth pathway with that power: RAS-ERK signalling stimulates purine synthesis directly and within minutes, because ERK2 - but not ERK1 - phosphorylates the purine synthesis enzyme PFAS at Thr619. Cells expressing a PFAS that cannot be phosphorylated make fewer purines, form fewer colonies and grow smaller tumors. Two points bound the mTOR claim: the control is posttranslational, so it acts far faster than transcription or translation, and it is a parallel input, so purine synthesis in a RAS-driven tumor is not read out from mTORC1 activity alone.
2017	M	mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability VAL2017 Hyperactive mTORC1 couples nucleotide synthesis to demand; imbalance drives replication stress in these cells.
2016	M	mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle BEN2016 mTORC1 promotes purine synthesis via ATF4-driven mitochondrial tetrahydrofolate metabolism.
2013	M	Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1 BEN2013 mTORC1-S6K1 stimulates de novo pyrimidine synthesis by phosphorylating CAD.
2013	M	Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis ROB2013 Quantitative phosphoproteomics show mTORC1 activates de novo pyrimidine synthesis.

Related entities

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Barton, O. (2026). Nucleotide synthesis [Entity page]. In Oliver's mTOR Atlas [Data set]. https://mtor-atlas.org/process/nucleotide-synthesis/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_process_nucleotide_synthesis,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}: Nucleotide synthesis},
  howpublished = {Entity page in a data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/process/nucleotide-synthesis/},
  doi          = {10.5281/zenodo.22059963}
}

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