Affinage

RRM1

Ribonucleoside-diphosphate reductase large subunit · UniProt P23921

Length
792 aa
Mass
90.1 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RRM1 encodes the catalytic large subunit of ribonucleotide reductase (RNR), which converts ribonucleotides to deoxyribonucleotides essential for DNA replication and repair; a conserved tryptophan residue mediates obligate heterodimerization with RRM2, and disruption of this interaction is embryonic lethal (PMID:26077802). CDK2/cyclin A phosphorylates RRM1 at Ser559 during S/G2 phase to enhance RNR activity and maintain dNTP pools, and loss of this phosphorylation causes replication stress and genomic instability (PMID:32712628). Independent of its reductase activity, RRM1 functions as a metastasis suppressor by transactivating PTEN to inhibit FAK signaling and cell migration (PMID:12687015, PMID:25638032), and promotes homologous recombination repair by chaperoning USP11 into the nucleus to stabilize E2F1 and upregulate RAD51AP1 transcription (PMID:39695160). Loss-of-function variants in RRM1 cause mitochondrial DNA depletion syndrome through impaired de novo nucleotide synthesis (PMID:35617047).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1995 Medium

    Identification of the RRM1 promoter architecture revealed how this housekeeping gene is transcriptionally regulated: a TATA-less minimal promoter driven by Sp1 binding.

    Evidence Reporter gene assays, EMSA, and antibody supershift in human cells

    PMID:7557993

    Open questions at the time
    • No in vivo chromatin validation (ChIP)
    • Other transcription factors contributing to cell-cycle-dependent regulation not identified
  2. 2003 High

    RRM1 was established as a metastasis suppressor acting through PTEN induction and FAK dephosphorylation, revealing a non-enzymatic tumor-suppressive function beyond nucleotide synthesis.

    Evidence Overexpression in human/mouse lung cancer cell lines, in vivo metastasis model, PTEN knockdown epistasis

    PMID:12687015

    Open questions at the time
    • Mechanism by which RRM1 transactivates PTEN unknown
    • Whether this function operates in normal physiology vs. cancer overexpression context unclear
  3. 2006 High

    Quantitative titration of RRM1 expression demonstrated it is the principal determinant of gemcitabine resistance, establishing the pharmacogenomic basis for gemcitabine response prediction.

    Evidence Engineered cell lines spanning 15-fold RRM1 expression range, IC50 dose-response for gemcitabine vs. platinum agents

    PMID:16966686

    Open questions at the time
    • In vivo dose-response relationship not established in this study
    • Resistance mechanism beyond competitive substrate binding not dissected
  4. 2013 Medium

    A kinome-wide synthetic lethality screen identified CHK1 as the kinase whose inhibition most potently synergizes with gemcitabine in high-RRM1 cells, revealing a replication checkpoint dependency.

    Evidence siRNA kinome screen (87 kinases), CHK1 inhibitor AZD7762 validation, inverse correlation of CHK1/RRM1 in 187 patient tumors

    PMID:23483975

    Open questions at the time
    • Direct physical interaction between RRM1 and CHK1 not demonstrated
    • Mechanism of inverse correlation in patient specimens not established
  5. 2014 Medium

    RRM1 depletion was shown to cause centrosomal amplification through CHK1 delocalization and CDK1 dependency, establishing a RRM1–CHK1–CDK1 axis in centrosome integrity maintenance.

    Evidence siRNA knockdown, hydroxyurea replication stress, CHK1/CDK1 double knockdown epistasis, centrosome counting

    PMID:24434653

    Open questions at the time
    • Whether centrosomal phenotype is direct or secondary to nucleotide depletion not resolved
    • Single lab without independent replication
  6. 2015 High

    Two key advances: (1) a conserved tryptophan in RRM1 was shown to be essential for RRM2 binding and mammalian viability, and (2) the PTEN-induction metastasis suppressor function was demonstrated to be independent of RNR catalytic activity using an enzymatically dead mutant.

    Evidence Mouse Rrm1-W688G knock-in (embryonic lethality, proteomic confirmation of lost RRM2 interaction); Y738F catalytic-dead RRM1 mutant overexpression with PTEN epistasis in colorectal cancer cells

    PMID:25638032 PMID:26077802

    Open questions at the time
    • Structural basis of how RRM1 protein (non-enzymatically) induces PTEN transcription unknown
    • Whether the W688 interaction surface has additional regulatory roles beyond heterodimerization not tested
  7. 2015 Medium

    MDM2 was identified as the E3 ligase for RRM1, mediating Lys48-linked polyubiquitination and proteasomal degradation, providing a regulated turnover mechanism downstream of MEK-AKT signaling.

    Evidence Co-immunoprecipitation, ubiquitination linkage assay, MG132 proteasome inhibition, pimasertib treatment in pancreatic cancer cells

    PMID:26228206

    Open questions at the time
    • Ubiquitination sites on RRM1 not mapped
    • Whether MDM2-mediated degradation operates under physiological conditions beyond drug treatment unclear
  8. 2020 High

    CDK2/cyclin A was identified as the kinase phosphorylating RRM1 at Ser559 during S/G2 phase, directly enhancing RNR enzymatic activity; loss of this modification causes replication stress and synergizes with ATR inhibition.

    Evidence Phosphorylation mapping, in vitro kinase assay, phosphomutant cell lines, dNTP pool measurement, γH2AX, ATR inhibitor epistasis

    PMID:32712628

    Open questions at the time
    • Whether additional phosphorylation sites regulate RRM1 activity not addressed
    • Structural mechanism by which S559 phosphorylation enhances catalysis not determined
  9. 2022 High

    Human loss-of-function variants in RRM1 were shown to cause mitochondrial DNA depletion syndrome, establishing RRM1 as a disease gene through impaired de novo nucleotide synthesis demonstrated in patient cells.

    Evidence Patient variant identification (p.N427K dominant, p.R381 recessive), mtDNA copy number in fibroblasts, dNTP pool analysis, molecular dynamics

    PMID:35617047

    Open questions at the time
    • Tissue-specific manifestations (why mitochondria are preferentially affected) not mechanistically explained
    • No rescue experiment with wild-type RRM1 in patient cells reported
  10. 2022 Medium

    RRM1 was linked to ferroptosis regulation through a USP11/MDM2–p53–p21–GPX4 signaling axis, where RRM1 depletion destabilizes p53 and reduces GPX4, promoting lipid peroxidation.

    Evidence siRNA knockdown, ROS and lipid peroxidation assays, ubiquitination assay for p53, GPX4 activity measurement

    PMID:35915092

    Open questions at the time
    • Direct physical interaction between RRM1 and USP11/MDM2 for p53 regulation not firmly established with reciprocal IP
    • Whether ferroptosis sensitivity is secondary to nucleotide depletion not excluded
  11. 2024 Medium

    A non-enzymatic DNA repair function was mechanistically delineated: RRM1 interacts with USP11 in the cytoplasm and, upon irradiation, is recruited to LaminB1 at the nuclear pore to facilitate USP11 nuclear entry, where USP11 deubiquitinates E2F1 to drive RAD51AP1 transcription and homologous recombination.

    Evidence Co-IP, nuclear fractionation, deletion mutagenesis (aa 731-793), HR reporter assay, RAD51AP1 transcription analysis

    PMID:39695160

    Open questions at the time
    • Single lab; domain deletion dominant-negative phenotype needs independent confirmation
    • Whether RRM1-USP11 interaction is regulated by post-translational modifications not tested
    • Stoichiometry and structural basis of RRM1–USP11–LaminB1 complex undefined
  12. 2024 Medium

    Translational control of RRM1 was revealed through diphthamide-dependent modulation of eEF2, where loss of diphthamide increases -1 frameshifting on RRM1 mRNA, reducing RRM1 protein and causing replication stress.

    Evidence Quantitative proteomics, -1 frameshifting reporter assay, DPH-deficient mammalian cell lines, replication stress markers

    PMID:39463834

    Open questions at the time
    • Specific frameshifting-prone sequences in RRM1 mRNA not mapped
    • Whether this translational regulation is physiologically modulated unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include: the structural/molecular mechanism by which RRM1 protein (independent of catalysis) activates PTEN transcription; how RRM1's enzymatic and non-enzymatic functions are coordinated in different cellular contexts; and the full spectrum of post-translational modifications regulating RRM1 stability, localization, and protein interactions.
  • No structural model of RRM1 non-enzymatic signaling complexes
  • Tissue-specific roles of RRM1 beyond cancer cell lines poorly characterized
  • Integration of enzymatic vs. scaffolding functions in normal physiology vs. disease not resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-69306 DNA Replication 3 R-HSA-73894 DNA Repair 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1643685 Disease 1
Partners
CDK2CHK1LMNB1MDM2PTENRRM2USP11
Complex memberships
Ribonucleotide reductase (RNR)

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Overexpression of RRM1 in human and mouse lung cancer cell lines induced PTEN expression, reduced phosphorylation of focal adhesion kinase (FAK), and suppressed migration, invasion, and metastasis formation. Increased PTEN expression was required for RRM1-induced suppression of cell motility and FAK phosphorylation, establishing RRM1 as a metastasis suppressor gene acting through PTEN induction. Overexpression in cancer cell lines, in vivo animal model, functional migration/invasion assays, PTEN knockdown epistasis Oncogene High 12687015
2006 In genetically engineered lung and breast cancer cell lines spanning a 15-fold RRM1 expression range, the gemcitabine IC50 showed a 100-fold range (highest with high RRM1 expression), while cisplatin/carboplatin IC50 showed only a 2-fold range, demonstrating that RRM1 level is the principal determinant of gemcitabine resistance. Genetically modified cell lines with increased/decreased RRM1 expression, IC50 determination by cytotoxicity assay Journal of clinical oncology High 16966686
1995 The TATA-less promoter of human RRM1 contains a minimal region (nt -195 to +3) sufficient for maximal reporter gene expression; EMSA and supershift assays identified Sp1 as a transcription factor that binds this promoter region in a sequence-specific manner, implicating Sp1 in RRM1 transcriptional regulation. Reporter gene transfection, electrophoretic mobility shift assay (EMSA), antibody supershift Genomics Medium 7557993
2015 A conserved tryptophan residue in RRM1 (mouse Rrm1-W688G equivalent) is essential for RRM1 binding to RRM2; homozygous Rrm1(WG/WG) mice are not viable even at earliest embryonic stages, demonstrating that RRM1-RRM2 interaction is essential for mammalian development. Proteomic analyses confirmed the mutation prevents RRM1-RRM2 complex formation. Mouse knock-in genetics, proteomics/mass spectrometry interaction analysis, embryonic viability assay Molecular and cellular biology High 26077802
2020 RRM1 is phosphorylated at Ser559 by CDK2/cyclin A during S/G2 phase; this phosphorylation enhances RNR enzymatic activity and is required for maintaining sufficient dNTPs during normal DNA replication. Loss of S559 phosphorylation causes DNA replication stress, double-strand breaks, and genomic instability. Combined targeting of RRM1 S559 phosphorylation and ATR kinase triggers lethal replication stress. Cell-cycle phosphorylation mapping, CDK2/cyclin A kinase assay, phosphomutant cell lines, dNTP pool measurement, DNA damage markers (γH2AX), ATR inhibitor epistasis Oncogene High 32712628
2022 RRM1 loss-of-function variants (dominant catalytic site variant p.N427K and recessive variants at p.R381) cause mitochondrial DNA depletion syndrome (MDDS) by impairing de novo nucleotide synthesis. Patient fibroblasts showed mtDNA depletion under cycling conditions, aberrant nucleoside diphosphate and dNTP pools, and mtDNA ribonucleotide incorporation. Human genetics (variant identification), molecular dynamics simulations, cultured primary patient fibroblasts, mtDNA copy number, dNTP pool analysis The Journal of clinical investigation High 35617047
2015 MEK1/2 inhibitor pimasertib reduces RRM1 protein levels via MDM2-mediated Lys48-linked polyubiquitination and proteasomal degradation; immunoprecipitation demonstrated enhanced MDM2-RRM1 interaction and polyubiquitination following pimasertib treatment, with AKT partially mediating this effect. Proteasome inhibitor MG132 blocked RRM1 reduction. Immunoprecipitation, immunoblotting, MG132 proteasome inhibition, ubiquitination assay, in vivo orthotopic pancreatic cancer model Clinical cancer research Medium 26228206
2014 RRM1 depletion (siRNA) induces cell-cycle arrest at replication phase along with severe DNA damage and centrosomal amplification. CHK1 depletion synergistically increased RRM1-depletion-induced centrosomal amplification; CHK1 was delocalized from the centrosome by RRM1 depletion during hydroxyurea treatment, and CDK1 was found essential for RRM1-depletion-induced centrosomal amplification, establishing a RRM1-CHK1-CDK1 axis maintaining centrosomal integrity. RNAi knockdown, hydroxyurea replication stress, centrosome counting, CHK1/CDK1 double knockdown epistasis Cancer letters Medium 24434653
2013 A synthetic lethality kinase screen identified CHK1 as the kinase with the most significant interaction with RRM1-dependent gemcitabine resistance. Synergism between CHK1 inhibition (AZD7762) and gemcitabine was observed specifically in cells with high RRM1 levels, while antagonism occurred in low RRM1 cells. In tumor specimens, CHK1 and RRM1 in situ protein levels were significantly and inversely correlated. siRNA kinome screen (87 kinases), cell viability assays, small-molecule CHK1 inhibitor (AZD7762), correlation analysis in 187 patient tumor specimens PloS one Medium 23483975
2015 RRM1 protein (non-enzymatically, as its RR-inactive Y738F mutant behaves identically) upregulates PTEN transactivation to inhibit colorectal cancer cell migration and invasion, reducing Akt phosphorylation and increasing E-cadherin expression; these effects were blocked by PTEN knockdown. Clinical specimens showed RRM1 protein level (but not RR enzymatic activity) correlated with PTEN expression and inversely with invasion/metastasis at stage T4. Wild-type and RR-inactive Y738F mutant overexpression, PTEN siRNA knockdown epistasis, RR activity assay, migration/invasion assays, clinical specimen analysis Tumour biology Medium 25638032
2021 RRM1 expression is increased in pancreatic cancer cells within 24 hours of gemcitabine exposure, with induction occurring predominantly in the cytoplasm; cytoplasmic RRM1 activation was related to cancer cell viability after gemcitabine treatment. Cancer cells lacking cytoplasmic RRM1 activation showed severe DNA damage. Histone acetyltransferase inhibition suppressed gemcitabine-induced RRM1 upregulation. Subcellular fractionation, immunohistochemistry, siRNA knockdown, HAT inhibitor treatment, cell viability assay PloS one Medium 34111175
2022 Knockdown of RRM1 promotes ferroptosis by increasing ROS and lipid peroxidation through regulation of GPX4 activity/expression. RRM1 controls p53 stability by regulating the deubiquitinating enzyme USP11 and ubiquitinating enzyme MDM2, affecting p53 ubiquitination; unstable p53 inhibits GPX4 via p21, providing a RRM1-USP11/MDM2-p53-p21-GPX4 signaling axis. siRNA knockdown, ROS/lipid peroxidation assays, ubiquitination assays, GPX4 activity measurement, western blotting for pathway components Cell death discovery Medium 35915092
2024 RRM1 interacts with USP11 in the cytoplasm; ionizing radiation-induced recruitment of RRM1 to LaminB1 facilitates USP11 binding to the nuclear pore complex (NPC) and promotes USP11 nuclear entry. Nuclear USP11 binds E2F1 and inhibits its ubiquitin-mediated degradation, enhancing transcription of the HR factor RAD51AP1. A RRM1 deletion mutant lacking amino acids 731-793 (required for USP11 interaction and LaminB1 recruitment) acts as dominant negative and abolishes this pathway. Co-immunoprecipitation, nuclear fractionation, ubiquitination assay, domain deletion mutagenesis, HR reporter assay, RAD51AP1 transcription analysis Cell death discovery Medium 39695160
2020 RRM1 knockdown in multiple myeloma cells triggered DNA damage response activation (γ-H2A.X, ATM, ATR, Chk1, Chk2, RAD51, 53BP1, BRCA1, BRCA2 upregulation/activation) and apoptosis via p53/p21/Noxa/Puma pathway in p53 wild-type cells; tumor growth of RRM1-knockdown cells was significantly reduced in murine xenograft model. siRNA knockdown, gene expression profiling, immunoblotting, in vivo xenograft model Clinical cancer research Medium 28442502
2020 LINC02535 cooperates with PCBP2 (which binds RRM1 mRNA) to enhance RRM1 mRNA stability in the cytoplasm; co-localization of LINC02535 and PCBP2 was confirmed, and their cooperation was required for RRM1-mediated DNA damage repair and EMT promotion in cervical cancer cells. RNA immunoprecipitation, mRNA stability assay, subcellular co-localization, siRNA knockdown, in vivo xenograft Journal of cellular physiology Medium 32324262
2024 YBX1 induces LRP1 transcription by binding to the LRP1 promoter, which alters β-catenin concentration and distribution; through TCF3, β-catenin then binds the RRM1 promoter to upregulate RRM1 expression, conferring gemcitabine resistance in pancreatic cancer cells. ChIP assay (YBX1 binding to LRP1 promoter, β-catenin/TCF3 binding to RRM1 promoter), β-catenin localization, in vitro and in vivo gemcitabine resistance assays Cancer letters Medium 39216548
2023 Reversible demethylation of the PDGFD promoter in gemcitabine-resistant pancreatic cancer cells leads to PDGFD upregulation, which activates STAT3 signaling in autocrine and paracrine manners to upregulate RRM1 expression, contributing to gemcitabine resistance. Whole genome reduced representation bisulfite sequencing, STAT3 inhibition, PDGFD knockdown/overexpression, RRM1 protein level measurement, in vitro and in vivo resistance models Cancer letters Medium 37321532
2024 Diphthamide modification of eEF2 modulates RRM1 mRNA translation via -1 frameshifting; loss of diphthamide in DPH-deficient mammalian cells reduces RRM1 protein levels and causally elevates DNA replication stress. Quantitative proteomics, computational profiling, -1 frameshifting reporter assay, DPH-deficient cell lines, DNA replication stress markers ACS central science Medium 39463834

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. The New England journal of medicine 400 17314339
2006 RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 286 16966686
2014 The crystal structure of TDP-43 RRM1-DNA complex reveals the specific recognition for UG- and TG-rich nucleic acids. Nucleic acids research 148 24464995
2010 The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. The Lancet. Oncology 145 21163702
2009 Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 144 19884554
2003 RRM1-induced metastasis suppression through PTEN-regulated pathways. Oncogene 127 12687015
2013 Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 120 23690416
2009 Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma. Oncogene 109 19543324
2012 Coaggregation of RNA-binding proteins in a model of TDP-43 proteinopathy with selective RGG motif methylation and a role for RRM1 ubiquitination. PloS one 104 22761693
2013 ERCC1 and RRM1: ready for prime time? Journal of clinical oncology : official journal of the American Society of Clinical Oncology 67 23401439
2011 RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for advanced non-small-cell lung cancer: a meta-analysis. Lung cancer (Amsterdam, Netherlands) 67 21889227
2013 Molecular mechanism of oxidation-induced TDP-43 RRM1 aggregation and loss of function. FEBS letters 64 23384725
2014 Synergic interplay of the La motif, RRM1 and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module. Nucleic acids research 55 25488812
2010 The immunohistochemical overexpression of ribonucleotide reductase regulatory subunit M1 (RRM1) protein is a predictor of shorter survival to gemcitabine-based chemotherapy in advanced non-small cell lung cancer (NSCLC). Lung cancer (Amsterdam, Netherlands) 53 20223551
2006 Ribonucleotide reductase M1 (RRM1) 2464G>A polymorphism shows an association with gemcitabine chemosensitivity in cancer cell lines. Pharmacogenetics and genomics 53 16708051
2012 The effect of the acid-sensitivity of 4-(N)-stearoyl gemcitabine-loaded micelles on drug resistance caused by RRM1 overexpression. Biomaterials 51 23261218
1999 Lung cancer and the human gene for ribonucleotide reductase subunit M1 (RRM1). Mammalian genome : official journal of the International Mammalian Genome Society 48 10441745
2015 The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1). Clinical cancer research : an official journal of the American Association for Cancer Research 47 26228206
2010 ERCC1 and RRM1 in the international adjuvant lung trial by automated quantitative in situ analysis. The American journal of pathology 47 21224045
2021 Structure of SRSF1 RRM1 bound to RNA reveals an unexpected bimodal mode of interaction and explains its involvement in SMN1 exon7 splicing. Nature communications 46 33462199
2012 Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection. Surgery 43 23253379
2007 An association between RRM1 haplotype and gemcitabine-induced neutropenia in breast cancer patients. The oncologist 43 17602053
2011 RT-PCR versus immunohistochemistry for correlation and quantification of ERCC1, BRCA1, TUBB3 and RRM1 in NSCLC. Lung cancer (Amsterdam, Netherlands) 42 21996087
2011 Preliminary indication of survival benefit from ERCC1 and RRM1-tailored chemotherapy in patients with advanced nonsmall cell lung cancer: evidence from an individual patient analysis. Cancer 39 22028294
2013 RRM1 domain of the splicing oncoprotein SRSF1 is required for MEK1-MAPK-ERK activation and cellular transformation. Carcinogenesis 38 23843040
2013 Just getting into cells is not enough: mechanisms underlying 4-(N)-stearoyl gemcitabine solid lipid nanoparticle's ability to overcome gemcitabine resistance caused by RRM1 overexpression. Journal of controlled release : official journal of the Controlled Release Society 37 23570983
2020 LINC02535 co-functions with PCBP2 to regulate DNA damage repair in cervical cancer by stabilizing RRM1 mRNA. Journal of cellular physiology 35 32324262
2013 Genetic polymorphisms of SLC28A3, SLC29A1 and RRM1 predict clinical outcome in patients with metastatic breast cancer receiving gemcitabine plus paclitaxel chemotherapy. European journal of cancer (Oxford, England : 1990) 34 24361227
2013 Phase II trial of customized first line chemotherapy according to ERCC1 and RRM1 SNPs in patients with advanced non-small-cell lung cancer. Lung cancer (Amsterdam, Netherlands) 33 24045016
2016 Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. Cancer chemotherapy and pharmacology 32 26842788
2017 Ribonucleotide Reductase Catalytic Subunit M1 (RRM1) as a Novel Therapeutic Target in Multiple Myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research 30 28442502
2013 RRM1 and RRM2 pharmacogenetics: association with phenotypes in HapMap cell lines and acute myeloid leukemia patients. Pharmacogenomics 30 24024897
2011 The expression of ERCC1, RRM1, and BRCA1 in breast cancer according to the immunohistochemical phenotypes. Journal of Korean medical science 30 21394302
2020 Exosome-Mediated Transfer of Long Noncoding RNA HOTAIR Regulates Temozolomide Resistance by miR-519a-3p/RRM1 Axis in Glioblastoma. Cancer biotherapy & radiopharmaceuticals 29 32721218
2022 Knockdown of RRM1 in tumor cells promotes radio-/chemotherapy induced ferroptosis by regulating p53 ubiquitination and p21-GPX4 signaling axis. Cell death discovery 28 35915092
2015 Trypanosoma brucei RRM1 is a nuclear RNA-binding protein and modulator of chromatin structure. mBio 27 25784696
2012 RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer. Cancer chemotherapy and pharmacology 26 22302408
2012 Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma? BMC cancer 26 22436573
2020 ALS-causing D169G mutation disrupts the ATP-binding capacity of TDP-43 RRM1 domain. Biochemical and biophysical research communications 25 32007267
2017 MicroRNA-1468-5p inhibits glioma cell proliferation and induces cell cycle arrest by targeting RRM1. American journal of cancer research 25 28469953
2008 mRNA expression of RRM1, ERCC1 and ERCC2 is not associated with chemosensitivity to cisplatin, carboplatin and gemcitabine in human lung cancer cell lines. Respirology (Carlton, Vic.) 25 18494946
2014 Expression of ERCC1, TYMS, TUBB3, RRM1 and TOP2A in patients with esophageal squamous cell carcinoma: A hierarchical clustering analysis. Experimental and therapeutic medicine 24 24926347
2013 Histology-related associations of ERCC1, RRM1, and TS biomarkers in patients with non-small-cell lung cancer: implications for therapy. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 24 23470290
2011 Differential effect of polymorphisms of CMPK1 and RRM1 on survival in advanced non-small cell lung cancer patients treated with gemcitabine or taxane/cisplatinum. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 24 21642870
2021 Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells. PloS one 23 34111175
2020 Cell-cycle-dependent phosphorylation of RRM1 ensures efficient DNA replication and regulates cancer vulnerability to ATR inhibition. Oncogene 23 32712628
2013 Predictive value of ERCC1 and RRM1 gene single-nucleotide polymorphisms for first-line platinum- and gemcitabine-based chemotherapy in non-small cell lung cancer patients. Oncology reports 23 23982437
2014 Expression of ERCC1, TYMS, RRM1, TUBB3, non-muscle myosin II, myoglobin and MyoD1 in lung adenocarcinoma pleural effusions predicts survival in patients receiving platinum-based chemotherapy. Molecular medicine reports 19 25573098
2011 Association of RRM1 -37A>C polymorphism with clinical outcome in colorectal cancer patients treated with gemcitabine-based chemotherapy. European journal of cancer (Oxford, England : 1990) 19 21220199
2024 YBX1 as a therapeutic target to suppress the LRP1-β-catenin-RRM1 axis and overcome gemcitabine resistance in pancreatic cancer. Cancer letters 18 39216548
2014 RRM1 modulates mitotane activity in adrenal cancer cells interfering with its metabolization. Molecular and cellular endocrinology 18 25497672
2013 A kinome screen identifies checkpoint kinase 1 (CHK1) as a sensitizer for RRM1-dependent gemcitabine efficacy. PloS one 18 23483975
2012 Expression of RRM1 and its association with resistancy to gemcitabine-based chemotherapy in advanced nasopharyngeal carcinoma. Chinese journal of cancer 18 22692073
2023 Reversible promoter demethylation of PDGFD confers gemcitabine resistance through STAT3 activation and RRM1 upregulation. Cancer letters 17 37321532
2014 Response to first-line chemotherapy in patients with non-small cell lung cancer according to RRM1 expression. PloS one 17 24647522
2017 Clinical significance of UGT1A1 polymorphism and expression of ERCC1, BRCA1, TYMS, RRM1, TUBB3, STMN1 and TOP2A in gastric cancer. BMC gastroenterology 16 28056823
2015 ERCC1 and RRM1 as a predictive parameter for non-small cell lung, ovarian or pancreas cancer treated with cisplatin and/or gemcitabine. Contemporary oncology (Poznan, Poland) 16 26557761
2023 RRM1 is mediated by histone acetylation through gemcitabine resistance and contributes to invasiveness and ECM remodeling in pancreatic cancer. International journal of oncology 15 36866763
2018 Oligomeric transition and dynamics of RNA binding by the HuR RRM1 domain in solution. Journal of biomolecular NMR 15 30535889
2015 Association of GSTP1 and RRM1 Polymorphisms with the Response and Toxicity of Gemcitabine-cisplatin Combination Chemotherapy in Chinese Patients with Non-small Cell Lung Cancer. Asian Pacific journal of cancer prevention : APJCP 15 26028097
2013 mRNA expression and clinical significance of ERCC1, BRCA1, RRM1, TYMS and TUBB3 in postoperative patients with non-small cell lung cancer. Asian Pacific journal of cancer prevention : APJCP 15 23803067
1995 Human gene for the large subunit of ribonucleotide reductase (RRM1): functional analysis of the promoter. Genomics 15 7557993
2022 RRM1 variants cause a mitochondrial DNA maintenance disorder via impaired de novo nucleotide synthesis. The Journal of clinical investigation 14 35617047
2020 Individualized chemotherapy guided by the expression of ERCC1, RRM1, TUBB3, TYMS and TOP2A genes versus classic chemotherapy in the treatment of breast cancer: A comparative effectiveness study. Oncology letters 14 33240427
2016 Structure, Dynamics, and Interaction of p54(nrb)/NonO RRM1 with 5' Splice Site RNA Sequence. Biochemistry 14 27064654
2019 RRM1 predicts clinical outcome of high-and intermediate-risk non-muscle-invasive bladder cancer patients treated with intravesical gemcitabine monotherapy. BMC urology 13 31340801
2015 The relationship between RRM1 gene polymorphisms and effectiveness of gemcitabine-based first-line chemotherapy in advanced NSCLC patient. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 13 26650486
2013 The RRM1 domain of the poly(A)-binding protein from Saccharomyces cerevisiae is critical to control of mRNA deadenylation. Molecular genetics and genomics : MGG 13 23793387
2013 Gene aberrations of RRM1 and RRM2B and outcome of advanced breast cancer after treatment with docetaxel with or without gemcitabine. BMC cancer 13 24215511
2015 Non-enzymatic action of RRM1 protein upregulates PTEN leading to inhibition of colorectal cancer metastasis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 25638032
2014 RRM1 maintains centrosomal integrity via CHK1 and CDK1 signaling during replication stress. Cancer letters 12 24434653
2015 RRM1 expression is associated with the outcome of gemcitabine-based treatment of non-small cell lung cancer patients--a short report. Cellular oncology (Dordrecht, Netherlands) 11 26092210
1994 Human R1 subunit of ribonucleotide reductase (RRM1): 5' flanking region of the gene. Genomics 11 8188248
2021 Effects of rrm1 on NNV Resistance Revealed by RNA-seq and Gene Editing. Marine biotechnology (New York, N.Y.) 10 34735644
2018 RRM1 expression and the clinicopathological characteristics of patients with non-small cell lung cancer treated with gemcitabine. OncoTargets and therapy 10 30237724
2014 The identification of novel 5'-amino gemcitabine analogs as potent RRM1 inhibitors. Bioorganic & medicinal chemistry 10 24588962
2014 Multiplex real-time PCR for RRM1, XRCC1, TUBB3 and TS mRNA for prediction of response of non-small cell lung cancer to chemoradiotherapy. Asian Pacific journal of cancer prevention : APJCP 10 24935362
2014 Expression of ERCC1, RRM1 and LRP in non-small cell lung cancers and their influence on chemotherapeutic efficacy of gemcitabine concomitant with nedaplatin. Asian Pacific journal of cancer prevention : APJCP 10 25227833
2012 Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1. Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 10 23359225
2021 Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells. International journal of molecular sciences 9 33921102
2019 WGS-based telomere length analysis in Dutch family trios implicates stronger maternal inheritance and a role for RRM1 gene. Scientific reports 9 31822713
2018 DNA Binding Induces a Nanomechanical Switch in the RRM1 Domain of TDP-43. The journal of physical chemistry letters 9 29924934
2017 Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer. International journal of molecular medicine 9 28949378
2016 A randomized phase II trial of ERCC1 and RRM1 mRNA expression-based chemotherapy versus docetaxel/carboplatin in advanced non-small cell lung cancer. Cancer chemotherapy and pharmacology 9 26811178
2015 A Single Conserved Residue Mediates Binding of the Ribonucleotide Reductase Catalytic Subunit RRM1 to RRM2 and Is Essential for Mouse Development. Molecular and cellular biology 9 26077802
2016 RRM1 *151A>T, RRM1 -756T>C, and RRM1 -585T>Gis associated with increased susceptibility of lung cancer in Chinese patients. Cancer medicine 8 27335251
2011 Production and characterization of a novel protease from Bacillus sp. RRM1 under solid state fermentation. Journal of microbiology and biotechnology 8 21715970
2024 Loss of Diphthamide Increases DNA Replication Stress in Mammalian Cells by Modulating the Translation of RRM1. ACS central science 7 39463834
2023 A missense mutation in RRM1 contributes to animal tameness. Science advances 7 37352351
2016 RRM1, RRM2 and ERCC2 Gene Polymorphisms in Coronary Artery Disease. In vivo (Athens, Greece) 7 27566080
2014 Predictive role of RRM1 and BRCA1 mRNA expression on the clinical outcome of advanced non-small cell lung cancer. Genetics and molecular research : GMR 7 25078585
2021 RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin. BMC cancer 6 34353292
2024 RRM1 promotes homologous recombination and radio/chemo-sensitivity via enhancing USP11 and E2F1-mediated RAD51AP1 transcription. Cell death discovery 5 39695160
2023 Nicotine promotes epithelial to mesenchymal transition and gemcitabine resistance via hENT1/RRM1 signalling in pancreatic cancer and chemosensitizing effects of Embelin-a naturally occurring benzoquinone. The Science of the total environment 5 38163613
2022 Platycodon D-induced A549 Cell Apoptosis through RRM1-Regulated p53/VEGF/ MMP2 Pathway. Anti-cancer agents in medicinal chemistry 5 35088678
2022 Association between TOP2A, RRM1, HER2, ERCC1 expression and response to chemotherapy in patients with non-muscle invasive bladder cancer. Heliyon 5 35711974
2022 Allosteric mechanism for SL RNA recognition by polypyrimidine tract binding protein RRM1: An atomistic MD simulation and network-based study. International journal of biological macromolecules 5 36058398
2022 Personalized Prescription of Chemotherapy Based on Assessment of mRNA Expression of BRCA1, RRM1, ERCC1, TOP1, TOP2α, TUBβ3, TYMS, and GSTP1 Genes in Tumors Compared to Standard Chemotherapy in the Treatment of Non-Small-Cell Lung Cancer. Journal of personalized medicine 5 36294786
2015 (1)H, (15)N and (13)C chemical shift assignments of the La motif and RRM1 from human LARP6. Biomolecular NMR assignments 5 25896032
2013 The tailored chemotherapy based on RRM1 immunohistochemical expression in patients with advanced non-small cell lung cancer. Cancer biomarkers : section A of Disease markers 5 24595080