ArticleNature metabolism2024
ASS1 metabolically contributes to the nuclear and cytosolic p53-mediated DNA damage response.
Article in Nature metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Arginine metabolism, polyamine homeostasis and ferroptosis in cancer: Molecular links and therapeutic opportunities (Review).Molecular medicine reports · 2026Review
- ASS1-derived argininosuccinate promotes purine nucleoside synthesis in B cell acute lymphoblastic leukaemia.Nature metabolism · 2026Article
- Deleterious in vitro effects of ammonia and accumulated urea cycle amino acids on leukocyte DNA: assessment of the antioxidant effects of N-acetylcysteine and L-carnitine.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- Molecular characterization of the uterotrophic assay: temporal gene expression changes in uterus and pituitary gland following ethinylestradiol.Archives of toxicology · 2026Article
- Arginine dependency in omental metastasis of epithelial ovarian cancer reveals a therapeutic vulnerability.Cell death & disease · 2026Article
- Ligand-Dependent and -Independent Functions of Activation Function 1 of Progesterone Receptor in Genome-Wide Gene Regulation and in Cell Proliferation and Apoptosis of Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Cetuximab co-treatment with KRAS G12C inhibitors fulzerasib and sotorasib in human KRAS G12C non-small cell lung cancer cells.Cell death discovery · 2026Article
- Hallmarks of nuclear metabolism: implications for genome integrity, nuclear signaling, and therapeutic targeting.npj metabolic health and disease · 2026Review
- Article
- The role of ASS1 in mouse embryonic stem cell differentiation into mesendoderm lineages.Stem cell research & therapy · 2025Article
- Evaluation of the Anticancer Properties of Lamellar Alkaloid Drivatives Extracted from the TunicateMolecules (Basel, Switzerland) · 2025Article
- ASS1 is a hub gene and possible therapeutic target for regulating metabolic dysfunction-associated steatotic liver disease modulated by a carbohydrate-restricted diet.Molecular diversity · 2025Article
- The arginine metabolism battlefield: how metabolite exchange in the tumor microenvironment shapes an immunosuppressive ecosystem.Cancer biology & medicine · 2025Article
- Dynamic crosstalk between amino acid metabolism and cancer drug efficacy: From mechanisms to therapeutic opportunities.iScience · 2025Review
- Metabolomic analysis reveals key changes in amino acid metabolism in colorectal cancer patients.Amino acids · 2025Article
- Etoposide-induced protein 2.4 homolog promotes argininosuccinate synthase 1 and cancer cell survival upon arginine deprivation.Cellular & molecular biology letters · 2025Article
- Arginine: at the crossroads of nitrogen metabolism.The EMBO journal · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
29 authors.
Funding
Abstract
Downregulation of the urea cycle enzyme argininosuccinate synthase (ASS1) in multiple tumors is associated with a poor prognosis partly because of the metabolic diversion of cytosolic aspartate for pyrimidine synthesis, supporting proliferation and mutagenesis owing to nucleotide imbalance. Here, we find that prolonged loss of ASS1 promotes DNA damage in colon cancer cells and fibroblasts from subjects with citrullinemia type I. Following acute induction of DNA damage with doxorubicin, ASS1 expression is elevated in the cytosol and the nucleus with at least a partial dependency on p53; ASS1 metabolically restrains cell cycle progression in the cytosol by restricting nucleotide synthesis. In the nucleus, ASS1 and ASL generate fumarate for the succination of SMARCC1, destabilizing the chromatin-remodeling complex SMARCC1-SNF5 to decrease gene transcription, specifically in a subset of the p53-regulated cell cycle genes. Thus, following DNA damage, ASS1 is part of the p53 network that pauses cell cycle progression, enabling genome maintenance and survival. Loss of ASS1 contributes to DNA damage and promotes cell cycle progression, likely contributing to cancer mutagenesis and, hence, adaptability potential.
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