ArticleNature communications2019
Acetylation regulates ribonucleotide reductase activity and cancer cell growth.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 79 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Elevated dNTP Pool Levels Impair Homologous Recombination and Enhance Glioblastoma Sensitivity to Irradiation and Temozolomide.International journal of molecular sciences · 2026Article
- Subtype-specific clinical significance of RRM1 and RRM2 expression in non-small cell lung cancer: a TCGA-based analysis.Genes & genomics · 2026Article
- Adaptive Regulation of dNTP Homeostasis Confers Osimertinib Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.Cancer research · 2026Article
- Redox stress agents strongly enhance mutagenesis during horizontal gene transfer in bacteria and leave distinct mutational and metabolic footprints.bioRxiv : the preprint server for biology · 2026Article
- Integrated bioinformatics analysis identifies cuproptosis and ferroptosis gene signatures via subgroup clustering: Prognostic and therapeutic implications in breast cancer.Biochemistry and biophysics reports · 2025Article
- DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferationWorld journal of gastrointestinal oncology · 2025Article
- Novel Insights into the Molecular Mechanisms of Chicken Breast Muscle Development by Integrating Non-Coding RNA and mRNA Profiles.International journal of molecular sciences · 2025Article
- Potential role of lysine acetylation in the stepwise adaptation ofMicrobiology spectrum · 2025Article
- RRM1 O-GlcNAcylation inhibition suppresses pancreatic cancer via TK1-mediated replication stress.Cancer gene therapy · 2025Article
- KAT7-acetylated YBX1 promotes hepatocellular carcinoma proliferation by reprogramming nucleotide metabolism.BMC cancer · 2025Article
- DNA damage repair-related methylated genes RRM2 and GAPDH are prognostic biomarkers associated with immunotherapy for lung adenocarcinoma.Genetics and molecular biology · 2025Article
- Cyclin Y interacts with Chk1 to activate RRM2/STAT3 signaling and promotes radioresistance in non-small cell lung cancer.International journal of biological sciences · 2025Article
- Role of BRCA1 in glioblastoma etiology.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Membrane RRM2-positive cells represent a malignant population with cancer stem cell features in intrahepatic cholangiocarcinoma.Journal of experimental & clinical cancer research : CR · 2024Article
- Proteomics Identifies LUC7L3 as a Prognostic Biomarker for Hepatocellular Carcinoma.Current issues in molecular biology · 2024Article
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- RRM2 promotes the proliferation of chicken myoblasts, inhibits their differentiation and muscle regeneration.Poultry science · 2024Article
- FBXO31 is upregulated by METTL3 to promote pancreatic cancer progression via regulating SIRT2 ubiquitination and degradation.Cell death & disease · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleoside diphosphates (dNDPs) to provide dNTP precursors for DNA synthesis. Here, we report that acetylation and deacetylation of the RRM2 subunit of RNR acts as a molecular switch that impacts RNR activity, dNTP synthesis, and DNA replication fork progression. Acetylation of RRM2 at K95 abrogates RNR activity by disrupting its homodimer assembly. RRM2 is directly acetylated by KAT7, and deacetylated by Sirt2, respectively. Sirt2, which level peak in S phase, sustains RNR activity at or above a threshold level required for dNTPs synthesis. We also find that radiation or camptothecin-induced DNA damage promotes RRM2 deacetylation by enhancing Sirt2-RRM2 interaction. Acetylation of RRM2 at K95 results in the reduction of the dNTP pool, DNA replication fork stalling, and the suppression of tumor cell growth in vitro and in vivo. This study therefore identifies acetylation as a regulatory mechanism governing RNR activity.
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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.