Affinage

POLR1A

DNA-directed RNA polymerase I subunit RPA1 · UniProt O95602

Round 2 corrected
Length
1720 aa
Mass
194.8 kDa
Annotated
2026-04-28
102 papers in source corpus 14 papers cited in narrative 14 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

POLR1A encodes the largest catalytic subunit (RPA194/A190) of RNA Polymerase I, the enzyme dedicated to ribosomal DNA transcription and ribosome biogenesis. The subunit harbors conserved zinc-binding and catalytic regions shared with other multi-subunit RNA polymerases, is essential for cell viability, and is recruited to rDNA promoters through RRN3–SL1 interactions; its transcriptional output is positively regulated by SIRT7-mediated deacetylation of the associated subunit PAF53 (PMID:2830265, PMID:11250903, PMID:24207024). Heterozygous loss-of-function variants in POLR1A cause acrofacial dysostosis (Cincinnati type) with p53-dependent neural crest cell apoptosis, while biallelic missense variants cause hypomyelinating leukodystrophy linked to aberrant rRNA processing and endoplasmic reticulum stress (PMID:25913037, PMID:36917474, PMID:37075751). A nucleolar–mitochondrial signaling axis has been identified in which POLR1A controls TFAM expression via ATF4, suppressing mitophagy-dependent labile iron release and ferroptosis (PMID:40669210).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1988 High

    Identification of the largest Pol I subunit gene (RPA190) as a single-copy essential gene with conserved polymerase motifs established POLR1A as the catalytic core of rDNA transcription.

    Evidence Yeast gene disruption, sequencing, and dot-matrix comparison revealing conserved regions I–VI shared with Pol II/III largest subunits and E. coli β'

    PMID:2830265 PMID:3054507

    Open questions at the time
    • No three-dimensional structure of the A190 subunit or Pol I holoenzyme at this time
    • Mechanism of promoter recognition and subunit assembly unknown
  2. 1990 High

    Conditional depletion of RPA190 demonstrated that rRNA synthesis is rate-limiting for ribosome production and that excess ribosomal proteins are degraded post-translationally, establishing the cellular consequences of Pol I loss.

    Evidence Galactose-promoter conditional expression of RPA190 in yeast with pulse-chase labeling and polysome analysis

    PMID:2183018

    Open questions at the time
    • Post-translational degradation pathway for excess ribosomal proteins not identified
    • Mammalian equivalence of this regulatory coupling not yet tested
  3. 2001 High

    Discovery that hRRN3 defines a transcription-competent Pol I subpopulation and bridges Pol I to the SL1 promoter-recognition complex resolved how Pol I is recruited to rDNA promoters.

    Evidence Affinity purification, reciprocal co-IP, in vitro transcription reconstitution, and ChIP in human cells

    PMID:11250903

    Open questions at the time
    • Structural basis of the RRN3–Pol I and RRN3–SL1 interfaces unknown
    • Regulation of RRN3 availability as a rate-limiting step not fully dissected
  4. 2002 High

    Live-cell FRAP showed that Pol I assembles at rDNA promoters from individual subunits through metastable intermediates rather than as a preformed holoenzyme, redefining the assembly paradigm.

    Evidence GFP-tagged Pol I subunits in mammalian cell lines, quantitative FRAP with kinetic modeling

    PMID:12446911

    Open questions at the time
    • Identity and order of metastable assembly intermediates not resolved biochemically
    • Stoichiometry of on-chromatin versus off-chromatin pools unclear
  5. 2006 High

    SIRT7 was identified as a nucleolar activator of Pol I transcription that associates with active rRNA genes, linking NAD+-dependent signaling to rDNA output.

    Evidence Co-IP, ChIP at rDNA, SIRT7 knockdown and overexpression with Pol I transcription readouts

    PMID:16618798

    Open questions at the time
    • Direct enzymatic substrate of SIRT7 on the Pol I machinery not yet identified
    • Whether SIRT7 acts directly on POLR1A or on an accessory factor unknown
  6. 2013 High

    SIRT7 was shown to deacetylate PAF53 at K373, establishing a specific post-translational switch that tunes Pol I–rDNA occupancy; stress-induced SIRT7 release causes PAF53 hyperacetylation and Pol I shutdown.

    Evidence In vitro deacetylation assay, acetylation-site mutagenesis, ChIP, RNA immunoprecipitation, stress-relocalization assays

    PMID:22586326 PMID:24207024

    Open questions at the time
    • Whether SIRT7 also deacetylates POLR1A/RPA194 itself not tested
    • Upstream kinase/phosphatase inputs that trigger SIRT7 nucleolar release not defined
  7. 2015 High

    Human heterozygous POLR1A mutations were shown to cause acrofacial dysostosis (Cincinnati type), with zebrafish modeling demonstrating that Polr1a haploinsufficiency impairs ribosome biogenesis and induces p53-dependent apoptosis selectively in neural crest cells.

    Evidence Human exome sequencing, zebrafish morpholino/mutant, ribosome biogenesis assays, p53 pathway analysis, skeletal staining

    PMID:25913037

    Open questions at the time
    • Why neural crest cells are selectively sensitive to Pol I haploinsufficiency remains unclear
    • Contribution of individual ribosomal RNA species versus global ribosome shortage not dissected
  8. 2023 High

    An allelic series of POLR1A variants was linked to a broad phenotypic spectrum (craniofacial, cardiac, neurodevelopmental) and conditional mouse knockouts demonstrated cell-autonomous apoptosis in neural crest, second heart field, and forebrain lineages, expanding the disease paradigm beyond craniofacial dysostosis. Separately, biallelic variants were shown to cause leukodystrophy via aberrant rRNA processing and ER stress.

    Evidence Human cohort sequencing, CRISPR knock-in and Cre-lox conditional mice, patient fibroblast rRNA processing and ER stress assays

    PMID:28051070 PMID:36917474 PMID:37075751

    Open questions at the time
    • How specific missense variants differentially affect Pol I catalytic activity versus assembly remains unclear
    • Whether ER stress in leukodystrophy is a direct consequence of unfolded protein accumulation from reduced ribosome output not proven
    • No rescue experiments with wild-type POLR1A in mouse or patient cells reported
  9. 2025 Medium

    A nucleolar–mitochondrial signaling axis was uncovered in which POLR1A controls TFAM expression through ATF4, restraining mitophagy-dependent labile iron release and conferring ferroptosis resistance — revealing a non-canonical function linking Pol I activity to mitochondrial quality control.

    Evidence POLR1A knockdown/CX-5461 inhibition, TFAM expression analysis, mitophagy and labile iron assays, lipid peroxidation readouts, in vivo xenograft synergy with GPX4 inhibition

    PMID:40669210

    Open questions at the time
    • Single-lab finding; independent replication needed
    • Whether ATF4 induction is a direct transcriptional consequence of reduced rRNA or a secondary stress response is unresolved
    • Relevance of this axis to POLR1A-associated human diseases not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis for variant-specific catalytic defects, the tissue-selective vulnerability mechanisms in ribosomopathy phenotypes, and whether the POLR1A–ATF4–TFAM ferroptosis axis operates in vivo under physiological Pol I stress.
  • No high-resolution structure of human Pol I with disease-associated POLR1A variants
  • Tissue-specific ribosome biogenesis thresholds not quantified
  • In vivo significance of ferroptosis regulation by POLR1A unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 4 GO:0003677 DNA binding 2
Localization
GO:0005730 nucleolus 5 GO:0005634 nucleus 2
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-1643685 Disease 4 R-HSA-8953854 Metabolism of RNA 3
Partners
ATF4PAF53RRN3SIRT7TAFI110TAFI63TFAMUBF
Complex memberships
RNA Polymerase I

Evidence

Reading pass · 14 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The yeast RPA190 gene encodes the largest subunit (A190, 186 kDa) of RNA polymerase I; the gene is unique in the haploid genome and essential for cell viability. Sequence analysis revealed conserved homology regions (I–VI) shared with E. coli beta' and the largest subunits of RNA Pol II and Pol III, including a conserved N-terminal zinc-binding (DNA-binding) motif. A190 lacks the heptapeptide CTD repeat present in the Pol II large subunit and contains two unique hydrophilic insertion domains. Gene isolation, Southern hybridization, gene disruption, nuclease S1 mapping, DNA sequencing, dot-matrix sequence comparison The Journal of biological chemistry High 2830265
1988 Temperature-sensitive mutations in yeast RPA190 (the POLR1A ortholog) cause defective rRNA accumulation and reduced RNA polymerase I activity in vitro at the non-permissive temperature, while 5S RNA synthesis is relatively unaffected. Fine-structure mapping showed that two ts mutations (rpa190-1 and rpa190-5) cluster in the conserved zinc-binding region I; rpa190-3 maps to a previously unidentified highly conserved segment between regions III and IV and appears to reduce enzyme levels; rpa190-2 creates a UGA nonsense codon. In vitro hydroxylamine mutagenesis, plasmid shuffle, pulse-labeling of RNA, partial purification of RNA Pol I and in vitro assay, fine-structure mapping, DNA sequencing Molecular and cellular biology High 3054507
1990 Conditional depletion of RPA190 (yeast POLR1A ortholog) via galactose-promoter control causes preferential loss of rRNA synthesis; ribosomal protein accumulation subsequently decreases to match the reduced rRNA synthesis rate, largely through post-translational degradation of excess r-proteins rather than transcriptional repression of r-protein mRNAs. An exception is L32 pre-mRNA splicing, which is feedback-inhibited when rRNA decreases. Galactose-promoter conditional expression system, pulse-chase labeling, polysome analysis, Northern blotting Molecular and cellular biology High 2183018
2001 hRRN3 defines a transcriptionally competent subpopulation of RNA Polymerase I (Pol I beta) and is required for Pol I recruitment to rDNA promoters. hRRN3 physically interacts with the SL1 subunits TAF(I)110 and TAF(I)63; blocking this interaction prevents Pol I recruitment to the promoter. hRRN3 can also be found in Pol I holoenzyme complexes capable of autonomous transcription. Affinity purification, co-immunoprecipitation, in vitro transcription assay, chromatin immunoprecipitation The EMBO journal High 11250903
2002 In living cells, mammalian RNA Polymerase I components are recruited to ribosomal genes as distinct subunits and assembly occurs via metastable intermediates rather than as a preformed holoenzyme. In vivo elongation time of the polymerase was determined by computational modeling of FRAP data; incorporation of components into the assembling polymerase is inefficient. In vivo fluorescence microscopy (FRAP), computational modeling of imaging data, stable cell lines expressing GFP-tagged Pol I subunits Science High 12446911
2006 SIRT7 is a nucleolar protein that associates with RNA Polymerase I at active rRNA genes. Overexpression of SIRT7 increases Pol I-mediated transcription; knockdown of SIRT7 or inhibition of its catalytic activity reduces Pol I association with rDNA and decreases Pol I transcription. SIRT7 depletion stops cell proliferation and triggers apoptosis. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), RNAi knockdown, overexpression, cell proliferation and apoptosis assays Genes & development High 16618798
2012 Functional proteomics of SIRT7 confirmed its interaction with RNA Pol I and upstream binding factor (UBF) and revealed association with chromatin remodeling complexes (B-WICH complex members: Mybbp1a, WSTF, SNF2h). SIRT7 knockdown reduces RNA Pol I protein levels (but not mRNA), implicating SIRT7 in stabilization of the Pol I machinery. EGFP-tagged SIRT7 affinity purification, mass spectrometry, SRM-like quantitative proteomics with SILAC, confocal microscopy, reciprocal immunoaffinity precipitation, siRNA knockdown Molecular & cellular proteomics High 22586326
2013 SIRT7 deacetylates PAF53 (a subunit of RNA Polymerase I) at lysine 373; acetylation of PAF53 by CBP reduces Pol I–rDNA occupancy and transcription, while SIRT7-mediated deacetylation promotes it. Under stress, SIRT7 is released from nucleoli in an RNA-dependent manner, leading to PAF53 hyperacetylation and reduced Pol I transcription. SIRT7 nucleolar retention requires binding to nascent pre-rRNA. In vitro deacetylation assay, acetylation-site mutagenesis, ChIP, RNA immunoprecipitation, fluorescence microscopy, stress-induced SIRT7 relocalization assays Molecular cell High 24207024
2013 RNA Polymerase I-specific transcription factors (including SL1/TIF-IB, UBF, RRN3/TIF-IA) guide Pol I to the rDNA promoter and contribute to multiple rounds of initiation, promoter escape, elongation, and termination. Accessory factors integrate transcriptional activity with metabolic demands, and rDNA chromatin organization/epigenetic state impinges on Pol I output. Deregulated Pol I transcription is a feature of cancer. Review integrating biochemical reconstitution, ChIP, and mutagenesis studies from multiple labs Sub-cellular biochemistry High 23150253
2015 Heterozygous mutations in POLR1A (encoding the largest subunit of RNA Polymerase I, RPA194) cause acrofacial dysostosis, Cincinnati type. polr1a mutant zebrafish exhibit cranioskeletal anomalies; polr1a loss of function leads to perturbed ribosome biogenesis, p53-dependent cell death, and deficiency of neural-crest-derived skeletal precursor cells, resulting in craniofacial anomalies. Human exome sequencing, zebrafish polr1a morpholino/mutant model, ribosome biogenesis assays, p53 pathway analysis, skeletal staining American journal of human genetics High 25913037
2017 A homozygous missense variant in POLR1A (c.2801C>T, p.Ser934Leu), encoding RPA194 (the largest subunit of RNA Pol I), causes complex leukodystrophy with neurodegeneration in humans. Skin fibroblasts from affected individuals showed decreased nucleolar RPA194 protein, linking POLR1A dysfunction to disrupted nucleolar function and leukodystrophy. Linkage analysis, exome sequencing, immunofluorescence of RPA194 in patient fibroblasts, segregation analysis European journal of human genetics Medium 28051070
2023 Heterozygous pathogenic POLR1A variants cause a phenotypic spectrum including craniofacial anomalies, neurodevelopmental abnormalities, and structural cardiac defects. In vitro studies showed that individual variants have variable effects on ribosomal RNA synthesis and nucleolar morphology. Conditional mutagenesis in mice demonstrated that loss of Polr1a in neural crest cells, second heart field, or forebrain precursors causes cell-autonomous apoptosis and embryonic malformations in the corresponding tissues. Human cohort sequencing, in vitro rRNA synthesis assays, nucleolar morphology analysis, CRISPR-Cas9 knock-in mice, conditional (Cre-lox) mutagenesis in specific developmental lineages, embryonic phenotyping American journal of human genetics High 37075751
2023 A homozygous POLR1A missense variant (p.Thr642Asn) causes hypomyelinating leukodystrophy with cerebellar atrophy. In vitro experiments in patient fibroblasts demonstrated that mutant POLR1A leads to aberrant rRNA processing and degradation, abnormal nucleolar homeostasis, abnormal protein homeostasis, and endoplasmic reticulum stress responses. Exome sequencing, patient fibroblast culture, rRNA processing assays, nucleolar morphology, proteomics, ER stress marker analysis Brain High 36917474
2025 POLR1A (the catalytic subunit of RNA Polymerase I) controls TFAM expression via the transcription factor ATF4, and this POLR1A–ATF4–TFAM axis inhibits mitophagy and limits mitophagy-dependent labile Fe2+ release, thereby preventing Fe2+-driven lipid peroxidation and ferroptosis. Disruption of POLR1A or TFAM leads to Fe2+ accumulation and increased sensitivity to ferroptosis inducers. CX-5461 (a Pol I inhibitor) synergizes with GPX4 blockade to induce ferroptotic cell death in vitro and in vivo. POLR1A knockdown/inhibition (CX-5461), TFAM expression analysis, mitophagy assays, labile iron pool measurements, lipid peroxidation assays, GPX4 combination experiments, in vivo xenograft models Redox biology Medium 40669210

Source papers

Stage 0 corpus · 102 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2004 A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway. Nature cell biology 841 14743216
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. Genes & development 478 16618798
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2007 Functional specialization of beta-arrestin interactions revealed by proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 360 17620599
2002 A kinetic framework for a mammalian RNA polymerase in vivo. Science (New York, N.Y.) 345 12446911
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2020 UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination. Nature cell biology 168 32807901
2013 Repression of RNA polymerase I upon stress is caused by inhibition of RNA-dependent deacetylation of PAF53 by SIRT7. Molecular cell 167 24207024
1998 Genetic analysis of yeast RPA1 reveals its multiple functions in DNA metabolism. Genetics 166 9539419
2020 Synthetic Lethal and Resistance Interactions with BET Bromodomain Inhibitors in Triple-Negative Breast Cancer. Molecular cell 159 32416067
2001 hRRN3 is essential in the SL1-mediated recruitment of RNA Polymerase I to rRNA gene promoters. The EMBO journal 155 11250903
2015 Cell-fate determination by ubiquitin-dependent regulation of translation. Nature 149 26399832
2012 Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription. Molecular & cellular proteomics : MCP 145 22586326
2013 Basic mechanisms in RNA polymerase I transcription of the ribosomal RNA genes. Sub-cellular biochemistry 142 23150253
2005 Mutation in Rpa1 results in defective DNA double-strand break repair, chromosomal instability and cancer in mice. Nature genetics 126 15965476
2020 Global crotonylome reveals CDYL-regulated RPA1 crotonylation in homologous recombination-mediated DNA repair. Science advances 116 32201722
1988 RPA190, the gene coding for the largest subunit of yeast RNA polymerase A. The Journal of biological chemistry 101 2830265
2008 Cellular functions of human RPA1. Multiple roles of domains in replication, repair, and checkpoints. The Journal of biological chemistry 96 18469000
2001 Rfc4 interacts with Rpa1 and is required for both DNA replication and DNA damage checkpoints in Saccharomyces cerevisiae. Molecular and cellular biology 95 11340166
2015 PTEN regulates RPA1 and protects DNA replication forks. Cell research 78 26403191
1987 Structural analysis of the Drosophila rpA1 gene, a member of the eucaryotic 'A' type ribosomal protein family. Nucleic acids research 70 3103101
2017 PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair. Cell reports 67 28854354
2015 Acrofacial Dysostosis, Cincinnati Type, a Mandibulofacial Dysostosis Syndrome with Limb Anomalies, Is Caused by POLR1A Dysfunction. American journal of human genetics 65 25913037
2008 Immunolocalization of Kim-1, RPA-1, and RPA-2 in kidney of gentamicin-, mercury-, or chromium-treated rats: relationship to renal distributions of iNOS and nitrotyrosine. Toxicologic pathology 61 18441258
2018 RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression. Proceedings of the National Academy of Sciences of the United States of America 53 30309964
2009 Physical interaction between replication protein A (RPA) and MRN: involvement of RPA2 phosphorylation and the N-terminus of RPA1. Biochemistry 50 19586055
2022 Gain-of-function mutations in RPA1 cause a syndrome with short telomeres and somatic genetic rescue. Blood 49 34767620
2017 Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA replication via downregulating RPA1. British journal of cancer 48 29024939
2017 UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair. Cell reports 46 28854355
1997 Expression of an ortholog of replication protein A1 (RPA1) is induced by gibberellin in deepwater rice. Proceedings of the National Academy of Sciences of the United States of America 46 9275237
1988 Isolation and characterization of temperature-sensitive mutations in RPA190, the gene encoding the largest subunit of RNA polymerase I from Saccharomyces cerevisiae. Molecular and cellular biology 45 3054507
1990 Conditional expression of RPA190, the gene encoding the largest subunit of yeast RNA polymerase I: effects of decreased rRNA synthesis on ribosomal protein synthesis. Molecular and cellular biology 39 2183018
2009 Differences in immunolocalization of Kim-1, RPA-1, and RPA-2 in kidneys of gentamicin-, cisplatin-, and valproic acid-treated rats: potential role of iNOS and nitrotyrosine. Toxicologic pathology 34 19535489
2003 MEC1-dependent phosphorylation of yeast RPA1 in vitro. DNA repair 33 14642562
2015 Metalaxyl Resistance in Phytophthora infestans: Assessing Role of RPA190 Gene and Diversity Within Clonal Lineages. Phytopathology 30 26551315
1997 Cell cycle regulation of RPA1 transcript levels in the trypanosomatid Crithidia fasciculata. Nucleic acids research 27 9241242
2016 miR-30a can inhibit DNA replication by targeting RPA1 thus slowing cancer cell proliferation. The Biochemical journal 25 27208176
2018 Differential RPA-1 and RAD-51 recruitment in vivo throughout the C. elegans germline, as revealed by laser microirradiation. Nucleic acids research 24 29244155
2017 Severe neurodegenerative disease in brothers with homozygous mutation in POLR1A. European journal of human genetics : EJHG 23 28051070
2011 Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome. PLoS genetics 23 21901111
2018 Oncogene RPA1 promotes proliferation of hepatocellular carcinoma via CDK4/Cyclin-D pathway. Biochemical and biophysical research communications 22 29477843
2018 RPA1 downregulation enhances nasopharyngeal cancer radiosensitivity via blocking RAD51 to the DNA damage site. Experimental cell research 22 30144445
2023 Loss of RPA1 Impairs Peripheral T Cell Homeostasis and Exacerbates Inflammatory Damage through Triggering T Cell Necroptosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 36721037
2020 Rpa1 mediates an immune response to avrRpm1Psa and confers resistance against Pseudomonas syringae pv. actinidiae. The Plant journal : for cell and molecular biology 19 31849122
2018 Analysis of RPA190 revealed multiple positively selected mutations associated with metalaxyl resistance in Phytophthora infestans. Pest management science 19 29457681
1998 Nuleclear extracts of Crithidia fasciculata contain a factor(s) that binds to the 5'-untranslated regions of TOP2 and RPA1 mRNAs containing sequences required for their cell cycle regulation. The Journal of biological chemistry 19 9726980
2020 Radioresistance, DNA Damage and DNA Repair in Cells With Moderate Overexpression of RPA1. Frontiers in genetics 18 32849834
2019 Genetic variants in RPA1 associated with the response to oxaliplatin-based chemotherapy in colorectal cancer. Journal of gastroenterology 18 30923916
2022 RPA1 controls chromatin architecture and maintains lipid metabolic homeostasis. Cell reports 17 35830798
2013 The natural absence of RPA1N domain did not impair Leishmania amazonensis RPA-1 participation in DNA damage response and telomere protection. Parasitology 17 23388105
1994 High-resolution genomic mapping of the three human replication protein A genes (RPA1, RPA2, and RPA3). Genomics 17 8020972
2012 Physical and functional interactions of Caenorhabditis elegans WRN-1 helicase with RPA-1. Biochemistry 16 22257160
2023 POLR1A variants underlie phenotypic heterogeneity in craniofacial, neural, and cardiac anomalies. American journal of human genetics 15 37075751
2016 RpA1 ameliorates symptoms of mutant ataxin-1 knock-in mice and enhances DNA damage repair. Human molecular genetics 15 28173122
2014 RPA-1 from Leishmania amazonensis (LaRPA-1) structurally differs from other eukaryote RPA-1 and interacts with telomeric DNA via its N-terminal OB-fold domain. FEBS letters 14 25451229
2005 Loss of RPA1 induces Chk2 phosphorylation through a caffeine-sensitive pathway. FEBS letters 13 15620706
2020 A multi-approach analysis highlights the relevance of RPA-1 as a telomere end-binding protein (TEBP) in Leishmania amazonensis. Biochimica et biophysica acta. General subjects 11 32222548
2015 RPA1 expression in esophageal carcinoma and its influence on radiosensitivity of esophageal carcinoma TE-1 cells. Panminerva medica 11 26824734
2020 Replication Protein A (RPA1, RPA2 and RPA3) expression in gastric cancer: correlation with clinicopathologic parameters and patients' survival. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 7 32862594
2025 POLR1A inhibits ferroptosis by regulating TFAM-mediated mitophagy and iron homeostasis. Redox biology 6 40669210
2020 The RPA190-pc gene participates in the regulation of metalaxyl sensitivity, pathogenicity and growth in Phytophthora capsici. Gene 6 32860897
2023 A homozygous POLR1A variant causes leukodystrophy and affects protein homeostasis. Brain : a journal of neurology 4 36917474
2023 Germline landscape of RPA1, RPA2 and RPA3 variants in pediatric malignancies: identification of RPA1 as a novel cancer predisposition candidate gene. Frontiers in oncology 4 37869077
2025 RPA1 protects DNA damage-induced PANoptosis in limb development. Science advances 3 40834068
2024 Cinchophen induces RPA1 related DNA damage and apoptosis to impair ENS development of zebrafish. Ecotoxicology and environmental safety 3 38306819
2023 Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. PLoS genetics 3 37200372
2023 UBQLN1 deficiency mediates telomere shortening and IPF through interacting with RPA1. PLoS genetics 3 37463174
2025 In and out of Replication Stress: PCNA/RPA1-Based Dynamics of Fork Stalling and Restart in the Same Cell. International journal of molecular sciences 2 39859385
2025 Circular RNA circLIMK1-005 promotes the progression of lung adenocarcinoma by interacting with RPA1 protein to activate CDK4 signaling. Cell death discovery 1 40593477
2025 HAT1 functions as a lactyltransferase and mediates RPA1 lactylation to promote DNA repair and radioresistance in lung adenocarcinoma. Cell death & disease 1 41271679
2024 CDC20 Holds Novel Regulation Mechanism in RPA1 during Different Stages of DNA Damage to Induce Radio-Chemoresistance. International journal of molecular sciences 1 39125953
2024 Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer. Frontiers in immunology 1 39660144
2021 Remote Homology Detection Identifies a Eukaryotic RPA DBD-C-like DNA Binding Domain as a Conserved Feature of Archaeal Rpa1-Like Proteins. Frontiers in molecular biosciences 1 34355021
1999 Molecular cloning, developmental expression, and cellular localization of the 70-kDa RPA-1 subunit of Drosophila melanogaster. DNA and cell biology 1 10619604
2026 Ascites circRNA ASCOR Drives Platinum Resistance of High-Grade Serous Ovarian Cancer by Facilitating RPA1 Nuclear Translocation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41677375
2026 HAT1 as a Lactyltransferase to Promote DNA Repair Through RPA1 Lactylation in Glioblastoma. International journal of biological sciences 0 41694603
2026 RNF185 orchestrates replication fork restart and homologous recombination through temporal RPA1 ubiquitination switching. Cancer letters 0 41997286
2025 Role and mechanism of RPA1 in the development and progression of glioma. Experimental and therapeutic medicine 0 40630228
2025 Phosphorylation of RNF213 by ATM-mediated ubiquitination of RPA1 regulates homologous recombination repair and chemosensitivity. Cell death & disease 0 41120267
2025 RPA1, RFC1, and POLE Expression in Clear Cell Renal Cell Carcinoma: Immune and Clinical Relevance. Anticancer research 0 41318151
2025 Oncometabolite fumarate impairs ATR-CHK1 signaling by succinating RPA1 in Fumarate Hydratase-deficient renal cell carcinoma cells. bioRxiv : the preprint server for biology 0 41427347
2023 Comprehensive mutational analysis of the checkpoint signaling function of Rpa1/Ssb1 in fission yeast. bioRxiv : the preprint server for biology 0 36945624
2021 Quantifying the Affinity of Trypanosoma cruzi RPA-1 to the Single-Stranded DNA Overhang of the Telomere Using Surface Plasmon Resonance. Methods in molecular biology (Clifton, N.J.) 0 33847961
2021 [Effects of RPA1 down-regulation on the invasion and migration and cell cycle of human nasopharyngeal carcinoma CNE-2R cells with radio resistance]. Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 0 34816659
2017 Feeling Stressed under the Sun? RPA1 Acetylation to the Rescue. Cell reports 0 28854353