ArticleOncogene2020
Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 25 citations in OpenAlex.
- Herpes simplex virus type 2 induces S-phase entry and arrest to regulate the cell cycle for efficient replication.The Journal of general virology · 2026Article
- RRM1 competes with NEDD4 to stabilize USP19 by blocking K387 ubiquitination and suppresses autophagy-mediated chemoresistance in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- CD74 deficiency protects against doxorubicin cardiotoxicity through RRM2-mediated regulation of ferroptosis.Acta pharmaceutica Sinica. B · 2026Article
- Abemaciclib Inhibits Retinoblastoma Tumor Growth by Targeting CDK1/2.Investigative ophthalmology & visual science · 2026Article
- Targeted metabolism creates possibilities for lung cancer treatment in the precision tumor era.Respiratory research · 2026Review
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Integrating multi-omics data and machine learning to identify endocrine disrupting chemicals targeting key ccRCC-related genes.Discover oncology · 2025Article
- DEAD/H-box RNA helicase 10 promotes pancreatic cancer cell proliferationWorld journal of gastrointestinal oncology · 2025Article
- RRM1 O-GlcNAcylation inhibition suppresses pancreatic cancer via TK1-mediated replication stress.Cancer gene therapy · 2025Article
- Clinical application and drug resistance mechanism of gemcitabine.Frontiers in cell and developmental biology · 2025Review
- Understanding the interplay between dNTP metabolism and genome stability in cancer.Disease models & mechanisms · 2024Review
- Synergistic Effect of a Combination of Proteasome and Ribonucleotide Reductase Inhibitors in a Biochemical Model of the YeastInternational journal of molecular sciences · 2024Article
- A comprehensive analysis of ribonucleotide reductase subunit M2 for carcinogenesis in pan-cancer.PloS one · 2024Article
- SL-scan identifies synthetic lethal interactions in cancer using metabolic networks.Scientific reports · 2023Article
- RRM2 Alleviates Doxorubicin-Induced Cardiotoxicity through the AKT/mTOR Signaling Pathway.Biomolecules · 2022Article
- High expression of RRM2 mediated by non-coding RNAs correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.Frontiers in medicine · 2022Article
- Still no Rest for the Reductases: Ribonucleotide Reductase (RNR) Structure and Function: An Update.Sub-cellular biochemistry · 2022Review
- RRM2 Mediates the Anti-Tumor Effect of the Natural Product Pectolinarigenin on Glioblastoma Through Promoting CDK1 Protein Degradation by Increasing Autophagic Flux.Frontiers in oncology · 2022Article
- Effects of rrm1 on NNV Resistance Revealed by RNA-seq and Gene Editing.Marine biotechnology (New York, N.Y.) · 2021Article
- USP5 facilitates non-small cell lung cancer progression through stabilization of PD-L1.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribonucleotide reductase (RNR) catalyzes the rate-limiting step of de novo synthesis of deoxyribonucleotide triphosphates (dNTPs) building blocks for DNA synthesis, and is a well-recognized target for cancer therapy. RNR is a heterotetramer consisting of two large RRM1 subunits and two small RRM2 subunits. RNR activity is greatly stimulated by transcriptional activation of RRM2 during S/G2 phase to ensure adequate dNTP supply for DNA replication. However, little is known about the cell-cycle-dependent regulation of RNR activity through RRM1. Here, we report that RRM1 is phosphorylated at Ser 559 by CDK2/cyclin A during S/G2 phase. And this S559 phosphorylation of RRM1enhances RNR enzymatic activity and is required for maintaining sufficient dNTPs during normal DNA replication. Defective RRM1 S559 phosphorylation causes DNA replication stress, double-strand break, and genomic instability. Moreover, combined targeting of RRM1 S559 phosphorylation and ATR triggers lethal replication stress and profound antitumor effects. Thus, this posttranslational phosphorylation of RRM1 provides an alternative mechanism to finely regulating RNR and therapeutic opportunities for cancer treatment.
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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.