Affinage

THOC1

THO complex subunit 1 · UniProt Q96FV9

Length
657 aa
Mass
75.7 kDa
Annotated
2026-06-10
44 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

THOC1 (Hpr1) is an essential subunit of the conserved THO/TREX ribonucleoprotein complex that couples RNA polymerase II transcription elongation with mRNP biogenesis and nuclear mRNA export while suppressing transcription-associated genomic instability (PMID:11060033, PMID:15870275). First identified in yeast as a factor whose loss drives extreme intrachromosomal hyperrecombination (PMID:2181275), Hpr1 was shown to operate within the RNA Pol II transcription machinery (PMID:8849885) and to be specifically required for elongation through long and G+C-rich sequences (PMID:9407037, PMID:11564888); the human ortholog associates with hyperphosphorylated elongating RNA Pol II, and its depletion likewise produces elongation defects (PMID:15870275). Hpr1 forms a stable four-subunit THO complex with Tho2, Mft1, and Thp2, deletion of any of which phenocopies hpr1Δ (PMID:11060033). The complex links nascent transcripts to export by acting in a common pathway with the RNA helicase Sub2/UAP56 (PMID:11463828, PMID:15870275) and by directly engaging the mRNA export receptor Mex67 through its UBA domain, a contact required for cotranscriptional Mex67 recruitment and proper mRNA export (PMID:17475778, PMID:19401465); Hpr1 further governs how much Mex67 is loaded onto nuclear mRNPs [PMID:bio_10.1101_2025.02.26.640412]. Loss of Hpr1/THO promotes co-transcriptional R-loop accumulation and DNA damage, although a separation-of-function allele establishes an R-loop-independent transcriptional role (PMID:16908536, PMID:19451165, PMID:32669125). THOC1 protein levels are controlled by ubiquitin-mediated proteasomal turnover linked to ongoing transcription, executed by the HECT E3 ligase Rsp5 in yeast and by NEDD4-1 in mammals (PMID:15713680, PMID:23460917). In mammals THOC1 is essential for early embryonic development and for inner cell mass viability (PMID:16705185), and it preferentially supports the gene-expression demands of proliferating and neoplastic cells: its depletion selectively kills oncogene-transformed cells and blocks transformation, prevents prostate cancer progression, and promotes growth of hepatocellular carcinoma, triple-negative breast cancer stem cells, and ovarian cancer (PMID:17638875, PMID:25296641, PMID:32669125, PMID:36330949, PMID:41372894). THOC1 also interacts with SIN3A to control histone deacetylation and telomeric R-loops (PMID:41496272) and binds U2AF2 to modulate Wnt/β-catenin signaling (PMID:41372894).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1990 Medium

    Established that HPR1 loss causes dramatic genomic instability, raising the question of what cellular process it protects.

    Evidence Complementation cloning and genetic double-mutant analysis with TOP1 in yeast

    PMID:2181275

    Open questions at the time
    • Molecular function not defined
    • C-terminal topoisomerase I homology not shown to confer enzymatic activity
  2. 1996 Medium

    Placed Hpr1 within the RNA polymerase II transcription machinery, reframing its genomic instability as a transcription-linked phenomenon.

    Evidence Suppressor genetics: RPB2 and SUA7/TFIIB mutants suppress hpr1 hyperrecombination

    PMID:8849885

    Open questions at the time
    • Did not identify the step of transcription affected
    • No physical association demonstrated
  3. 1997 High

    Defined Hpr1 as required for transcription elongation, particularly through difficult templates, linking elongation defects to recombination.

    Evidence Northern blot, primer extension, 6-azauracil sensitivity and lacZ reporter assays in yeast

    PMID:11564888 PMID:9407037

    Open questions at the time
    • Mechanism of elongation assistance not resolved
    • No complex partners yet identified
  4. 2000 High

    Identified the THO complex, establishing Hpr1 as one of four stable subunits whose coordinated function underlies elongation and genome stability.

    Evidence Affinity purification and reciprocal Co-IP with genetic phenotyping of all subunit deletions in yeast

    PMID:11060033

    Open questions at the time
    • Stoichiometry and architecture not determined
    • How the complex contacts Pol II unknown
  5. 2001 Medium

    Connected Hpr1/THO to mRNA export by linking it genetically to the RNA helicase Sub2/UAP56 in a common genome-stability pathway.

    Evidence Bidirectional high-copy suppressor genetics between HPR1 and SUB2 in yeast

    PMID:11463828

    Open questions at the time
    • Direct physical interaction not shown
    • Order of action in the pathway unresolved
  6. 2002 Medium

    Showed the THO complex contributes to transcription-coupled and global nucleotide excision repair, broadening its role in genome maintenance.

    Evidence UV sensitivity and T4 endonuclease V strand-specific repair assays in deletion mutants

    PMID:12000839

    Open questions at the time
    • Mechanistic basis of repair contribution unclear
    • Whether effect is direct or secondary to transcription defects unknown
  7. 2005 High

    Demonstrated conservation in humans, showing hHpr1/Thoc1 physically bridges elongating RNA Pol II and the export factor UAP56.

    Evidence Co-IP from cell extracts and RNAi depletion with elongation assays in human cells

    PMID:15870275

    Open questions at the time
    • Composition of human complex not fully defined
    • Direct vs bridged contacts not separated
  8. 2005 High

    Revealed that Hpr1 abundance is regulated by transcription-coupled ubiquitin-mediated turnover, introducing post-translational control of THO.

    Evidence In vivo and in vitro reconstituted ubiquitylation by Rsp5/Ubc4 in yeast

    PMID:15713680

    Open questions at the time
    • Functional consequence of turnover on complex assembly not directly measured
    • Ubiquitylation sites not mapped
  9. 2006 Medium

    Used a separation-of-function allele to mechanistically uncouple mRNP biogenesis/export defects from transcription-associated recombination.

    Evidence hpr1-101 point mutant analysis with Northern blot, in situ hybridization, and 2D gel replication assays in yeast

    PMID:16908536

    Open questions at the time
    • Structural basis of the separated functions unknown
    • Single allele defines the dissociation
  10. 2006 High

    Established that the mammalian ortholog is essential for early embryonic development, demonstrating in vivo necessity.

    Evidence Thoc1 knockout mouse with blastocyst hatching and outgrowth assays

    PMID:16705185

    Open questions at the time
    • Tissue-specific later roles not addressed by null
    • Molecular cause of ICM dependence not defined
  11. 2007 High

    Defined the structural basis of THO-export coupling, showing Hpr1 binds the Mex67 UBA domain to enable cotranscriptional export receptor recruitment.

    Evidence NMR structure of UBA-Mex67, binding measurements, ChIP and mRNA export assays in yeast

    PMID:17475778 PMID:19401465

    Open questions at the time
    • Dynamics of the Hpr1/ubiquitin/FG-nucleoporin handoff during export not fully resolved
  12. 2007 Medium

    Established a selective dependence of transformed cells on Thoc1, linking THO function to neoplastic transformation and DNA damage.

    Evidence RNAi in isogenic normal vs oncogene-transformed cells, apoptosis and γH2AX assays, transformation assay

    PMID:17638875

    Open questions at the time
    • Basis of cancer-cell selectivity not mechanistically defined
    • Single-lab cell-line comparison
  13. 2009 Medium

    Showed THO has an R-loop-independent transcriptional function, refining the model of how it suppresses instability.

    Evidence AID-based strand-specific mutation/recombination assays comparing hpr1-101 and hpr1Δ in yeast

    PMID:19451165

    Open questions at the time
    • Nature of the R-loop-independent activity unspecified
    • Generalization beyond AID system untested
  14. 2013 High

    Demonstrated evolutionary conservation of ubiquitin-mediated THOC1 regulation, with NEDD4-1 driving transcription-coupled degradation in mammals.

    Evidence In vitro ubiquitylation reconstitution and NEDD4-1/proteasome manipulation in human cells

    PMID:23460917

    Open questions at the time
    • Physiological signals triggering degradation not defined
    • Impact on human complex assembly not directly measured
  15. 2013 Medium

    Identified transcriptional control of THOC1 by the Nrf2/ARE axis under nitric oxide stress, linking its abundance to cancer-cell survival.

    Evidence Co-culture, NO donor/iNOS inhibitor, promoter-reporter and ARE mutagenesis, Nrf2 manipulation in cancer cells

    PMID:23688498

    Open questions at the time
    • Direct Nrf2 binding to the ARE not structurally confirmed
    • Link to Bcl-2 regulation mechanistically indirect
  16. 2014 Medium

    Used conditional knockouts to show lineage- and tumor-selective Thoc1 requirements in proliferating hematopoietic progenitors and prostate cancer.

    Evidence Inducible conditional knockout mice with lineage analysis and TRAMP prostate cancer model

    PMID:24830368 PMID:25296641

    Open questions at the time
    • Genes whose mis-expression drives the phenotype not pinpointed
    • Why proliferating cells are selectively sensitive unresolved
  17. 2016 Medium

    Connected Thoc1 to E2f-driven apoptotic gene expression downstream of Rb1 loss, providing a pathway context for its proliferation dependence.

    Evidence Rb1:Thoc1 compound conditional knockout mice with IHC, Western blot, and qRT-PCR of apoptotic genes

    PMID:27001308

    Open questions at the time
    • Whether Thoc1 acts directly on E2f gene expression unclear
    • Mechanism of selective support of these transcripts unknown
  18. 2020 Medium

    Linked THOC1 loss to R-loop-driven DNA damage and impaired cell-cycle progression in hepatocellular carcinoma, reinforcing its genome-protective and proliferative roles.

    Evidence shRNA knockdown, R-loop and γH2AX assays, cell cycle analysis, and xenografts

    PMID:32669125

    Open questions at the time
    • Direct vs indirect contribution to G2/M transition unresolved
    • Specific affected transcripts not identified
  19. 2020 High

    Established that thoc1 loss triggers p53-dependent apoptosis in sensory hair cells, defining a tissue context and downstream effector pathway.

    Evidence CRISPR knockout and morpholino zebrafish, mRNA rescue, RNA-seq, and p53 inhibition

    PMID:32776944

    Open questions at the time
    • Upstream trigger connecting THO dysfunction to p53 activation not defined
    • Relevance to mammalian hearing not established here
  20. 2024 Medium

    Identified a SIN3A interaction linking THOC1 to histone deacetylation and telomeric R-loop and telomere length control.

    Evidence CRISPR screen, Co-IP, R-loop immunofluorescence, telomere length analysis, and RNA-seq in glioblastoma cells

    PMID:41496272

    Open questions at the time
    • Direct vs complex-mediated SIN3A binding not separated
    • Causal order between deacetylation and R-loop changes unclear
  21. 2025 Medium

    Defined a direct THOC1-U2AF2 interaction that suppresses Wnt/β-catenin signaling, expanding THOC1 into splicing-factor regulation and oncogenic signaling.

    Evidence Co-IP, GST pull-down mapping the THOC1-340S site, immunofluorescence, and RNA-seq/KEGG in ovarian cancer cells

    PMID:41372894

    Open questions at the time
    • Mechanism by which U2AF2 binding alters Wnt output not resolved
    • Single-lab finding
  22. 2025 Medium

    Showed Hpr1 controls the quantity of Mex67 loaded onto nuclear mRNPs, with excess Mex67 itself impairing export, refining the export-coupling model.

    Evidence RNA immunoprecipitation and genetic overexpression suppression in Δhpr1 yeast (preprint)

    PMID:bio_10.1101_2025.02.26.640412

    Open questions at the time
    • Not yet peer-reviewed
    • Mechanism by which Hpr1 limits Mex67 loading unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How THOC1/THO selects and supports specific transcripts whose mis-expression underlies its essentiality in development and the heightened dependence of proliferating and cancer cells remains unresolved.
  • No defined set of THOC1-dependent transcripts that explains cancer-cell selectivity
  • No high-resolution structure of the human THO/TREX complex on Pol II
  • Whether SIN3A, U2AF2, and export functions are separable activities unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3 R-HSA-73894 DNA Repair 2
Partners
MEX67MFT1NEDD4SIN3ATHOC2THP2U2AF2UAP56
Complex memberships
THO complexTREX complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 HPR1 encodes a novel 752-amino acid protein with C-terminal homology to yeast topoisomerase I (TOP1); hpr1 null mutants show extremely high rates of intrachromosomal excision recombination, and hpr1 top1 double mutants grow very poorly, indicating functional interaction with Top1. Complementation cloning, sequence analysis, genetic double-mutant analysis Molecular and cellular biology Medium 2181275
1996 Mutations in RNA polymerase II components RPB2 and transcription initiation factor SUA7 (TFIIB) suppress hpr1 hyperrecombination, establishing by genetic epistasis that Hpr1 functions in the RNA polymerase II transcription machinery. Suppressor genetics, cloning, sequencing of soh (suppressor of hpr1) mutants Genetics Medium 8849885
1997 Hpr1 is required for transcriptional elongation; hpr1Δ cells cannot elongate transcription through the bacterial lacZ coding region (a long G+C-rich sequence) but elongate through yeast PHO5 normally; elongation defects are associated with hyperrecombination and genomic instability. Northern blot, primer extension, 6-azauracil sensitivity, lacZ reporter assays Genes & development High 9407037
2000 Hpr1 forms a stable nuclear oligomeric protein complex (the THO complex) with Tho2, Mft1, and a novel protein Thp2; reciprocal immunoprecipitation using HA-tagged Tho2 and anti-Mft1 antibodies confirmed the four-subunit complex; mft1Δ and thp2Δ cells phenocopy hpr1Δ with mitotic hyperrecombination and impaired transcription elongation. Affinity purification (His6-HA-tagged Tho2), reciprocal immunoprecipitation with anti-Mft1 antibodies, genetic phenotyping The EMBO journal High 11060033
2001 Hpr1 (as part of the THO complex) is preferentially required for transcription of long DNA sequences and G+C-rich sequences; the negative effect of sequences on transcription depends on distance from the promoter, and hyperrecombination correlates with transcriptional defects. GAL1-driven reporter assays with varying lacZ segments, LYS2 and YAT1 sequences; Northern blot; recombination assays Molecular and cellular biology Medium 11564888
2001 High-copy SUB2 (yeast homolog of human splicing factor UAP56/hUAP56) suppresses hpr1Δ genomic instability, and high-copy HPR1 suppresses sub2 conditional mutant instability; this bidirectional epistasis links Hpr1 to the RNA helicase Sub2 in a common pathway controlling genome stability. High-copy suppressor genetics, conditional allele analysis, reciprocal suppression Molecular and cellular biology Medium 11463828
2002 Deletion of HPR1 or THO2 impairs transcription-coupled nucleotide excision repair (TCR) as shown by T4 endonuclease V analysis of RPB2 transcribed strand repair; modest effects on global genome repair (GGR) also observed, indicating the THO complex contributes to both NER pathways. UV sensitivity assays, T4 endo V strand-specific repair analysis Nucleic acids research Medium 12000839
2005 Yeast Hpr1 is ubiquitylated by the HECT E3 ubiquitin ligase Rsp5 (with Ubc4 as the conjugating enzyme); Hpr1 degradation is enhanced at high temperature and is linked to ongoing RNA Pol II–mediated transcription; this ubiquitin-mediated turnover is specific to Hpr1 among THO subunits, suggesting Hpr1 ubiquitylation controls THO/TREX complex formation and mRNA export. In vivo ubiquitylation assays, in vitro ubiquitylation reconstitution with purified components, co-immunoprecipitation, genetic analysis The Journal of biological chemistry High 15713680
2005 Human hHpr1/p84/Thoc1 associates with elongating (hyperphosphorylated) RNA polymerase II and with the RNA splicing/export factor UAP56 in intact cells; depletion of hHpr1/p84/Thoc1 causes transcriptional elongation defects, establishing that the human protein physically links elongating RNA Pol II with RNA processing factors in a TREX-like complex. Co-immunoprecipitation from cell extracts, RNAi-mediated depletion, transcription elongation assays Molecular and cellular biology High 15870275
2006 Homozygous null Thoc1 mice are not viable; embryonic development arrests around implantation with blastocyst hatching and outgrowth defects; inner cell mass cells are especially dependent on Thoc1, demonstrating that the mammalian ortholog is essential for early embryonic development. Mouse knockout generation, embryo culture, in vitro blastocyst outgrowth assays Molecular and cellular biology High 16705185
2006 The hpr1-101 point mutant shows strong transcription defects and general mRNA export defects without triggering hyperrecombination or retarding replication fork progression, demonstrating that mRNP biogenesis impairment and transcription-associated recombination can be mechanistically uncoupled. Site-directed mutagenesis, Northern blot, in situ hybridization for mRNA export, 2D gel electrophoresis for replication fork analysis Molecular and cellular biology Medium 16908536
2007 The ubiquitin-associated (UBA) domain of mRNA export receptor Mex67 directly interacts with Hpr1; deletion or mutation of helix H4 of UBA-Mex67 decreases Hpr1-binding affinity but strengthens ubiquitin binding; Hpr1 interaction is required for UBA-Mex67 to bind polyubiquitin; in vivo, H4 deletion reduces cotranscriptional Mex67 recruitment to active genes and impairs mRNA export. Structural NMR of UBA domain, binding affinity measurements, in vivo chromatin immunoprecipitation, mRNA export assays Molecular biology of the cell High 17475778
2007 Depletion of human Thoc1 protein (pThoc1) causes apoptotic cell death specifically in neoplastically transformed cells, coincident with increased DNA damage (phospho-H2AX); normal cells are largely unaffected; normal cells lacking Thoc1 cannot be transformed by E1A and Ha-ras, implicating Thoc1 in neoplastic transformation. RNAi depletion in isogenic normal vs. oncogene-transformed cell lines, apoptosis assays, γH2AX immunostaining, transformation assay Cancer research Medium 17638875
2009 The hpr1-101 mutant impairs transcription and mRNP biogenesis without causing accumulation of co-transcriptional R-loops; AID-induced mutations in hpr1-101 occur at equal frequency on both DNA strands (unlike hpr1Δ where ssDNA from R-loops is the AID target), demonstrating that THO has an R-loop-independent transcriptional function. AID-induced mutation/recombination assays, strand-specific mutational analysis Nucleic acids research Medium 19451165
2009 NMR solution structure of the Mex67 UBA domain complexed with an FXFG nucleoporin peptide shows that Hpr1 and FG-repeat nucleoporins bind to overlapping sites on UBA-Mex67; Hpr1 binding allows UBA-Mex67 to interact with tetra-ubiquitin, whereas FXFG binding prevents mono- or tetra-ubiquitin binding. NMR solution structure determination, fluorescence resonance energy transfer (FRET)-based binding assays, NMR titration The Journal of biological chemistry High 19401465
2013 Human Thoc1 protein is poly-ubiquitinated by the NEDD4-1 E3 ubiquitin ligase and subsequently degraded by the proteasome; destabilization of Thoc1 upon transcriptional elongation inhibitor treatment is dependent on NEDD4-1, indicating evolutionary conservation of ubiquitin-mediated THO regulation between yeast (Rsp5) and mammals. In vitro ubiquitylation reconstitution with purified components, manipulation of NEDD4-1 levels in cells, proteasome inhibitor experiments PloS one High 23460917
2013 In cancer cells, nitric oxide (NO) produced by activated macrophages suppresses THOC1 expression via the Nrf2 transcription factor acting on an antioxidant response element (ARE) in the THOC1 promoter; overexpression of Thoc1 confers resistance to NO-mediated cytotoxicity; Thoc1 downregulation leads to Bcl-2 downregulation and apoptosis. Co-culture experiments, iNOS inhibitor, NO donor treatment, promoter-reporter assays, ARE mutagenesis, Nrf2 overexpression/knockdown Biochemical pharmacology Medium 23688498
2014 Conditional deletion of Thoc1 in the mouse hematopoietic system reveals that granulocyte-macrophage progenitors have a cell-autonomous requirement for Thoc1 to maintain growth and viability, while lymphoid lineages are not detectably affected under homeostatic conditions. Inducible conditional knockout mouse, bone marrow reconstitution, flow cytometry of hematopoietic lineages PloS one Medium 24830368
2014 Conditional deletion of Thoc1 in an autochthonous mouse prostate cancer model prevents cancer progression but has little effect on normal prostate tissue; prostate cancer cells deprived of Thoc1 show gene expression defects that compromise cell growth. Conditional knockout mouse in TRAMP prostate cancer model, histopathology, gene expression analysis Journal of the National Cancer Institute Medium 25296641
2016 Thoc1 deficiency in Rb1-null mice delays embryo death and reduces apoptosis in the brain; E2f protein levels and expression of E2f-regulated apoptotic genes (Apaf1, Bak1) are reduced in Rb1:Thoc1-deficient brain tissue, indicating that Thoc1 supports elevated E2f expression and downstream apoptotic gene expression triggered by Rb1 loss. Compound conditional knockout mouse, immunohistochemistry, Western blot, qRT-PCR of apoptotic gene expression Molecular and cellular biology Medium 27001308
2020 THOC1 knockdown leads to R-loop formation and DNA damage in hepatocellular carcinoma cells; THOC1 promotes G2/M cell cycle transition and HCC cell proliferation in vitro and in vivo. shRNA knockdown, R-loop immunofluorescence, γH2AX assay, colony formation, cell cycle analysis, xenograft mouse model Journal of experimental & clinical cancer research Medium 32669125
2020 THOC1 deficiency causes hair cell apoptosis via the p53 signaling pathway; in zebrafish, thoc1 knockout reduces hair cell numbers, and depletion of p53 or treatment with the p53 inhibitor Pifithrin-α significantly rescues hair cell loss; transcriptome sequencing showed upregulation of p53-associated genes in thoc1 mutants. CRISPR-Cas9 knockout zebrafish, morpholino knockdown, mRNA rescue injection, RNA sequencing, p53 inhibitor treatment, hair cell counting PLoS genetics High 32776944
2022 Thoc1 promotes cancer stem cell characteristics in triple-negative breast cancer by facilitating mRNA export of stemness-related genes; knockdown reduces cancer stem cell populations and mammosphere formation; overexpression of Thoc1 promotes TNBC malignancy; andrographolide reduces Thoc1 expression through suppression of NF-κB, an upstream transcriptional regulator of Thoc1. shRNA knockdown, overexpression, mammosphere assay, mRNA export assay, orthotopic mouse model, NF-κB reporter assay Biochemical pharmacology Medium 36330949
2024 THOC1 interacts with SIN3A (a histone deacetylase complex component); THOC1 knockdown leads to elevated R-loop levels, reduced histone deacetylation, increased telomeric R-loops, and shortened telomeres in glioblastoma cells. CRISPR knockout screen, co-immunoprecipitation, R-loop immunofluorescence, telomere length analysis, RNA sequencing Neoplasia (New York, N.Y.) Medium 41496272
2025 THOC1 directly binds U2AF2 (U2 snRNA auxiliary factor 2) via its THOC1-340S interaction site; this interaction regulates U2AF2 expression and mediates suppression of Wnt/β-catenin signaling, as evidenced by changes in cyclinD1, c-Myc, and β-catenin protein levels in ovarian cancer cells. Immunoprecipitation, GST pull-down, immunofluorescence, RNA sequencing, KEGG pathway analysis Cancer cell international Medium 41372894
2025 In Δhpr1 yeast cells, Nab2, Yra1 and Mex67 levels are increased in nuclear mRNPs; overexpression of Nab2 or Yra1 in Δhpr1 cells suppresses the mRNA export defect and reduces Mex67 levels in nuclear mRNPs to wild-type levels, indicating that Hpr1 regulates the amount of Mex67 loaded onto nuclear mRNPs and that excess Mex67 in mRNPs impairs nuclear mRNA export. RNA immunoprecipitation, mRNA export assays, genetic overexpression experiments in Δhpr1 cells bioRxivpreprint Medium bio_10.1101_2025.02.26.640412

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 A protein complex containing Tho2, Hpr1, Mft1 and a novel protein, Thp2, connects transcription elongation with mitotic recombination in Saccharomyces cerevisiae. The EMBO journal 257 11060033
1997 The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability. Genes & development 145 9407037
1996 Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae. Genetics 139 8849885
1990 HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene. Molecular and cellular biology 116 2181275
2001 Hpr1 is preferentially required for transcription of either long or G+C-rich DNA sequences in Saccharomyces cerevisiae. Molecular and cellular biology 99 11564888
2002 Cloning and characterization of the human heparanase-1 (HPR1) gene promoter: role of GA-binding protein and Sp1 in regulating HPR1 basal promoter activity. The Journal of biological chemistry 83 11779847
2011 Differential expression of THOC1 and ALY mRNP biogenesis/export factors in human cancers. BMC cancer 67 21329510
2005 The mRNA nuclear export factor Hpr1 is regulated by Rsp5-mediated ubiquitylation. The Journal of biological chemistry 62 15713680
2001 High-copy-number expression of Sub2p, a member of the RNA helicase superfamily, suppresses hpr1-mediated genomic instability. Molecular and cellular biology 53 11463828
2005 Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Molecular and cellular biology 52 15870275
1989 Genetic and molecular analysis of recombination events in Saccharomyces cerevisiae occurring in the presence of the hyper-recombination mutation hpr1. Genetics 48 2668113
2013 Inhibition of peroxisomal hydroxypyruvate reductase (HPR1) by tyrosine nitration. Biochimica et biophysica acta 47 23860243
1994 Characterization of mutations that suppress the temperature-sensitive growth of the hpr1 delta mutant of Saccharomyces cerevisiae. Genetics 44 7982575
2006 Thoc1/Hpr1/p84 is essential for early embryonic development in the mouse. Molecular and cellular biology 43 16705185
2007 Cancer cells and normal cells differ in their requirements for Thoc1. Cancer research 41 17638875
1993 Deamidation of HPr, a phosphocarrier protein of the phosphoenolpyruvate:sugar phosphotransferase system, involves asparagine 38 (HPr-1) and asparagine 12 (HPr-2) in isoaspartyl acid formation. The Journal of biological chemistry 39 8349654
1995 HPR1 encodes a global positive regulator of transcription in Saccharomyces cerevisiae. Molecular and cellular biology 38 7862161
1994 Increase in incidence of chromosome instability and non-conservative recombination between repeats in Saccharomyces cerevisiae hpr1 delta strains. Molecular & general genetics : MGG 36 7816031
2006 An hpr1 point mutation that impairs transcription and mRNP biogenesis without increasing recombination. Molecular and cellular biology 34 16908536
2020 Knockdown of THOC1 reduces the proliferation of hepatocellular carcinoma and increases the sensitivity to cisplatin. Journal of experimental & clinical cancer research : CR 32 32669125
1996 The yeast HRS1 gene encodes a polyglutamine-rich nuclear protein required for spontaneous and hpr1-induced deletions between direct repeats. Genetics 28 8849881
1996 Mutations in the yeast SRB2 general transcription factor suppress hpr1-induced recombination and show defects in DNA repair. Genetics 27 8844143
2007 Coordination of Hpr1 and ubiquitin binding by the UBA domain of the mRNA export factor Mex67. Molecular biology of the cell 23 17475778
2006 In vivo and in vitro degradation of heparan sulfate (HS) proteoglycans by HPR1 in pancreatic adenocarcinomas. Loss of cell surface HS suppresses fibroblast growth factor 2-mediated cell signaling and proliferation. The Journal of biological chemistry 23 17121850
2020 THOC1 deficiency leads to late-onset nonsyndromic hearing loss through p53-mediated hair cell apoptosis. PLoS genetics 22 32776944
2009 Structural requirements for the ubiquitin-associated domain of the mRNA export factor Mex67 to bind its specific targets, the transcription elongation THO complex component Hpr1 and nucleoporin FXFG repeats. The Journal of biological chemistry 21 19401465
1996 Mutations in GCR3, a gene involved in the expression of glycolytic genes in Saccharomyces cerevisiae, suppress the temperature-sensitive growth of hpr1 mutants. Genetics 21 8846890
1995 Isolation and genetic analysis of extragenic suppressors of the hyper-deletion phenotype of the Saccharomyces cerevisiae hpr1 delta mutation. Genetics 21 7705651
2014 The Thoc1 ribonucleoprotein and prostate cancer progression. Journal of the National Cancer Institute 19 25296641
2002 Defective nucleotide excision repair in yeast hpr1 and tho2 mutants. Nucleic acids research 15 12000839
2007 An allelic series for studying the mouse Thoc1 gene. Genesis (New York, N.Y. : 2000) 13 17211872
2022 Andrographolide suppresses the malignancy of triple-negative breast cancer by reducing THOC1-promoted cancer stem cell characteristics. Biochemical pharmacology 12 36330949
2013 The suppression of thoc1 in cancer cell apoptosis mediated by activated macrophages is nitric oxide-dependent. Biochemical pharmacology 12 23688498
2014 Thoc1 inhibits cell growth via induction of cell cycle arrest and apoptosis in lung cancer cells. Molecular medicine reports 10 24682263
2009 R-loops do not accumulate in transcription-defective hpr1-101 mutants: implications for the functional role of THO/TREX. Nucleic acids research 8 19451165
2016 Evaluating Effects of Hypomorphic Thoc1 Alleles on Embryonic Development in Rb1 Null Mice. Molecular and cellular biology 6 27001308
2014 The Thoc1 encoded ribonucleoprotein is required for myeloid progenitor cell homeostasis in the adult mouse. PloS one 6 24830368
2006 Combination gene therapy with p53 and Thoc1/p84 is more effective than either single agent in an animal model of human pancreatic adenocarcinoma. International journal of oncology 6 16465385
2004 Effects of mismatch repair and Hpr1 on transcription-stimulated mitotic recombination in the yeast Saccharomyces cerevisiae. DNA repair 5 15380099
2013 The Thoc1 encoded ribonucleoprotein is a substrate for the NEDD4-1 E3 ubiquitin protein ligase. PloS one 3 23460917
2024 THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression. bioRxiv : the preprint server for biology 1 39386597
2026 THOC1 complexes with SIN3A to regulate R-loops and promote glioblastoma progression. Neoplasia (New York, N.Y.) 0 41496272
2025 THOC1 binds to U2AF2 and regulates ovarian cancer progression through the beta-catenin / c-myc / cyclinD1 signaling pathway. Cancer cell international 0 41372894
2024 A patient with 18p11.32-p11.21 deletion have monaural deafness caused by an inadequate haplodose of THOC1: A case report. Medicine 0 39058882

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