ArticleCell reports2023
Arginine shortage induces replication stress and confers genotoxic resistance by inhibiting histone H4 translation and promoting PCNA ubiquitination.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 7 citations in OpenAlex.
- Influences of dietary guanidinoacetic acid supplementation on performance and proteins involved in milk fat and protein synthesis in dairy cows.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Influence of coated cobalamin on lactation performance, nutrient digestion, and proteins related to mammary epithelial cell proliferation and milk fatty acid synthesis in dairy cows.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Adaptation to Arginine Deprivation Leads to a More Aggressive, Therapy-Resistant Phenotype in HNSCC Cells.Biomolecules · 2025Article
- Impacts of dietary arginine supplementation on performance, nutrient digestion and expression of proteins related to milk fatty acid and casein synthesis in early lactating dairy cows.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
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15 authors at 5 institutions in 2 countries.
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Abstract
The arginine dependency of cancer cells creates metabolic vulnerability. In this study, we examine the impact of arginine availability on DNA replication and genotoxicity resistance. Using DNA combing assays, we find that limiting extracellular arginine results in the arrest of cancer cells at S phase and a slowing or stalling of DNA replication. The translation of new histone H4 is arginine dependent and influences DNA replication. Increased proliferating cell nuclear antigen (PCNA) occupancy and helicase-like transcription factor (HLTF)-catalyzed PCNA K63-linked polyubiquitination protect arginine-starved cells from DNA damage. Arginine-deprived cancer cells display tolerance to genotoxicity in a PCNA K63-linked polyubiquitination-dependent manner. Our findings highlight the crucial role of extracellular arginine in nutrient-regulated DNA replication and provide potential avenues for the development of cancer treatments.
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