ArticleMolecular cell2014
A divergent role of the SIRT1-TopBP1 axis in regulating metabolic checkpoint and DNA damage checkpoint.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 60 citations in OpenAlex.
- Computational Insights into SIRT1: Elucidating Mutational Impact on SIRT1-RECQL4 Structural Dynamics.Cell biochemistry and biophysics · 2026Article
- Centromere Protein I, a Cell Cycle Checkpoint Gene, Accelerates Tumor Progression via the Hippo Pathway and Mediates Immune Escape in Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2025Article
- Decoding replication stress responses through post-translational modifications.Nature chemical biology · 2025Review
- Selective interactions at pre-replication complexes categorize baseline and dormant origins.Nature communications · 2025Article
- Mono-ubiquitination of TopBP1 by PHRF1 enhances ATR activation and genomic stability.Nucleic acids research · 2025Article
- Article
- SIRT1 in the BNST modulates chronic stress-induced anxiety of male mice via FKBP5 and corticotropin-releasing factor signaling.Molecular psychiatry · 2023Article
- Article
- SIRT1 regulates DNA damage signaling through the PP4 phosphatase complex.Nucleic acids research · 2023Article
- Experimental Insights into the Interplay between Histone Modifiers and p53 in Regulating Gene Expression.International journal of molecular sciences · 2023Review
- Human Papillomavirus 16 E2 Interaction with TopBP1 Is Required for E2 and Viral Genome Stability during the Viral Life Cycle.Journal of virology · 2023Article
- Deubiquitinase OTUD6A promotes breast cancer progression by increasing TopBP1 stability and rendering tumor cells resistant to DNA-damaging therapy.Cell death and differentiation · 2022Article
- Sirtuin5 protects colorectal cancer from DNA damage by keeping nucleotide availability.Nature communications · 2022Article
- Convergence of SIRT1 and ATR signaling to modulate replication origin dormancy.Nucleic acids research · 2022Article
- Preventing excess replication origin activation to ensure genome stability.Trends in genetics : TIG · 2022Review
- Article
- PHF8-promoted TOPBP1 demethylation drives ATR activation and preserves genome stability.Science advances · 2021Article
- Article
- MTBP phosphorylation controls DNA replication origin firing.Scientific reports · 2021Article
- Biochemical analysis of TOPBP1 oligomerization.DNA repair · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
DNA replication is executed only when cells have sufficient metabolic resources and undamaged DNA. Nutrient limitation and DNA damage cause a metabolic checkpoint and DNA damage checkpoint, respectively. Although SIRT1 activity is regulated by metabolic stress and DNA damage, its function in these stress-mediated checkpoints remains elusive. Here we report that the SIRT1-TopBP1 axis functions as a switch for both checkpoints. With glucose deprivation, SIRT1 is activated and deacetylates TopBP1, resulting in TopBP1-Treslin disassociation and DNA replication inhibition. Conversely, SIRT1 activity is inhibited under genotoxic stress, resulting in increased TopBP1 acetylation that is important for the TopBP1-Rad9 interaction and activation of the ATR-Chk1 pathway. Mechanistically, we showed that acetylation of TopBP1 changes the conformation of TopBP1, thereby facilitating its interaction with distinct partners in DNA replication and checkpoint activation. Taken together, our studies identify the SIRT1-TopBP1 axis as a key signaling mode in the regulation of the metabolic checkpoint and the DNA damage checkpoint.
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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.