ArticleThe EMBO journal2022
Metabolic remodeling maintains a reducing environment for rapid activation of the yeast DNA replication checkpoint.
Article in The EMBO journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- RcAlb-PepII Perturbs the Proteomic Profile ofMicroorganisms · 2026Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- A Rfa1-MN-based system reveals new factors involved in the rescue of broken replication forks.PLoS genetics · 2025Article
- Novel insights into the effects of 5-hydroxymethfurural on genomic instability and phenotypic evolution using a yeast model.Applied and environmental microbiology · 2024Article
- Mec1-Rad53 Signaling Regulates DNA Damage-Induced Autophagy and Pathogenicity inJournal of fungi (Basel, Switzerland) · 2023Article
- A DNA damage-induced phosphorylation circuit enhances Mec1Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Metabolic remodeling maintains a reducing environment for rapid activation of the yeast DNA replication checkpoint.The EMBO journal · 2022Article
- Immune Landscape and Classification in Lung Adenocarcinoma Based on a Novel Cell Cycle Checkpoints Related Signature for Predicting Prognosis and Therapeutic Response.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nucleotide metabolism fuels normal DNA replication and is also primarily targeted by the DNA replication checkpoint when replication stalls. To reveal a comprehensive interconnection between genome maintenance and metabolism, we analyzed the metabolomic changes upon replication stress in the budding yeast S. cerevisiae. We found that upon treatment of cells with hydroxyurea, glucose is rapidly diverted to the oxidative pentose phosphate pathway (PPP). This effect is mediated by the AMP-dependent kinase, SNF1, which phosphorylates the transcription factor Mig1, thereby relieving repression of the gene encoding the rate-limiting enzyme of the PPP. Surprisingly, NADPH produced by the PPP is required for efficient recruitment of replication protein A (RPA) to single-stranded DNA, providing the signal for the activation of the Mec1/ATR-Rad53/CHK1 checkpoint signaling kinase cascade. Thus, SNF1, best known as a central energy controller, determines a fast mode of replication checkpoint activation through a redox mechanism. These findings establish that SNF1 provides a hub with direct links to cellular metabolism, redox, and surveillance of DNA replication in eukaryotes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.