Affinage

GTF2H1

General transcription factor IIH subunit 1 · UniProt P32780

Round 2 corrected
Length
548 aa
Mass
62.0 kDa
Annotated
2026-04-28
130 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GTF2H1 encodes the p62 subunit of the ten-subunit general transcription factor IIH (TFIIH), a complex that couples RNA polymerase II transcription initiation with nucleotide excision repair (NER). Within the ring-like TFIIH core architecture, p62 serves as a structural scaffold that contacts and regulates the XPD helicase, and its pleckstrin homology (PH) domain provides a common recruitment interface through which both XPC (global genome repair) and UVSSA (transcription-coupled repair) deliver TFIIH to DNA lesions (PMID:29069470, PMID:30860024). p62 also directly binds acidic transcriptional activation domains—including those of VP16, p53, and estrogen receptor α—thereby mediating activator-dependent stimulation of TFIIH-associated CDK7 kinase activity toward the RNA Pol II CTD (PMID:7935417, PMID:10949034). GTF2H1 expression is positively regulated by SWI/SNF ATPases BRG1 and BRM, and its downregulation destabilizes the entire TFIIH complex, impairing both transcription and NER and sensitizing cells to platinum-based chemotherapy (PMID:30287812).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1991 High

    The discovery that BTF2/TFIIH containing p62 is absolutely required for preinitiation complex formation and RNA Pol II transcription established GTF2H1 as a core component of the general transcription machinery.

    Evidence Biochemical purification from HeLa cells and in vitro transcription reconstitution

    PMID:1939143

    Open questions at the time
    • No distinction yet between p62's own contribution and that of the holoenzyme
    • No structural information on p62 within the complex
  2. 1994 High

    Identification of XPB and XPD helicases as TFIIH subunits, combined with antibody depletion of p62 abrogating NER, demonstrated that TFIIH—and p62 specifically—functions as a dual-purpose factor coupling transcription and DNA repair.

    Evidence Co-immunoprecipitation, antibody depletion, in vitro NER complementation, in vivo microinjection repair assays, and helicase/ATPase assays

    PMID:8152490 PMID:8157004 PMID:8194528 PMID:8465201

    Open questions at the time
    • Precise molecular role of p62 versus other core subunits in NER remained unclear
    • No atomic-resolution structural data
  3. 1994 High

    The finding that p62 is the direct binding target for acidic activation domains of VP16 and p53 revealed that TFIIH receives activator signals through GTF2H1, explaining how transcriptional activators stimulate initiation and elongation.

    Evidence GST pulldown, yeast two-hybrid, mutational correlation between VP16 transactivation and p62 binding across human and yeast systems

    PMID:7935417

    Open questions at the time
    • Structural basis for the activator–p62 interaction unknown
    • Whether p62 activator binding triggers allosteric changes in TFIIH enzymatic activities not resolved
  4. 1995 High

    Discovery that the CDK7/cyclin H kinase module (CAK) is a stable TFIIH component linked TFIIH-mediated CTD phosphorylation to the transcription cycle, while showing CTD kinase activity is dispensable for basal transcription itself.

    Evidence Co-purification of Cdk7/cyclin H with TFIIH, antibody inhibition of kinase and transcription, kinase-deficient TFIIH reconstitution

    PMID:7533895 PMID:7761469

    Open questions at the time
    • Whether CTD phosphorylation is required for activated transcription or elongation not settled
    • Mechanism of CAK attachment to the core complex unknown
  5. 2000 High

    EM imaging established the ring-like architecture of TFIIH, placing p62 within the core ring, while functional studies showed that p62 and XPD together contact the estrogen receptor α AF2 domain to direct CDK7-mediated phosphorylation of ERα-S118.

    Evidence Electron microscopy with immunolabeling of subunits; co-IP and in vitro kinase assay with ERα AF2 mutants

    PMID:10949034 PMID:11007478

    Open questions at the time
    • Atomic position of p62 within the ring not resolved
    • Whether p62–activator binding is a general mechanism for nuclear receptor coactivation unclear
  6. 2017 High

    NMR structure of the p62 PH domain bound to a UVSSA peptide, together with functional TCR assays, identified a common TFIIH recruitment mechanism used by both XPC (GGR) and UVSSA (TCR) through the same basic groove of the p62 PH domain.

    Evidence NMR structure of UVSSA–p62 PH domain complex, mutagenesis, TCR reconstitution in UVSSA-deficient cells

    PMID:29069470

    Open questions at the time
    • Full-length p62 structure in the context of holotranscription/repair complexes not yet available at high resolution
    • Whether other NER factors also contact the PH domain not tested
  7. 2017 High

    Cryo-EM of the yeast PIC and chemical-genetic dissection of CDK7 established the structural and functional framework for how TFIIH mediates promoter opening and CTD phosphorylation to regulate capping, pausing, and H3K4 methylation.

    Evidence Cryo-EM at 4.7–5.8 Å; analog-sensitive CDK7 cell lines with ChIP-seq, phospho-CTD pulldowns, and in vitro HMT assays

    PMID:28768201 PMID:29088706

    Open questions at the time
    • Human PIC structure at comparable resolution not yet achieved at this time
    • Direct contribution of p62 to PIC-level conformational changes unclear
  8. 2018 High

    SWI/SNF ATPases BRG1/BRM were shown to positively regulate GTF2H1 expression, and loss of GTF2H1 was sufficient to destabilize the TFIIH holocomplex and sensitize cells to DNA-damaging agents, establishing GTF2H1 as a rate-limiting factor for TFIIH function and a platinum-sensitivity determinant.

    Evidence BRM/BRG1 knockdown with GTF2H1 mRNA and protein quantification, TFIIH stability assay, UDS repair assay, UV/cisplatin sensitivity assay with GTF2H1 re-expression rescue in multiple cell lines

    PMID:30287812

    Open questions at the time
    • Mechanism by which SWI/SNF regulates GTF2H1 transcription not defined
    • Clinical validation of GTF2H1 as a predictive biomarker lacking
  9. 2019 High

    Near-atomic cryo-EM structures of human TFIIH core and TFIIH–XPA repair intermediates revealed that p62 directly contacts and regulates the XPD helicase, and showed how TFIIH conformationally switches between transcription and repair modes through XPA-driven CAK release and XPD pore opening.

    Evidence Cryo-EM at 3.7 Å (TFIIH core) and cryo-EM of TFIIH–XPA complex on DNA

    PMID:30860024 PMID:31253769

    Open questions at the time
    • How p62 allosterically modulates XPD helicase kinetics not biochemically dissected
    • Dynamics of the transcription-to-repair transition in living cells not captured
  10. 2023 High

    Cryo-EM structures of XPC–TFIIH–XPA complexes and single-molecule biochemistry defined the stepwise lesion handoff mechanism: XPA kinks DNA to reposition the lesion, XPB and XPD track opposite DNA strands, and XPG binding commits TFIIH to dsDNA unwinding and licenses incision upon lesion stalling.

    Evidence Cryo-EM of human XPC–Core7–XPA on damaged DNA; single-molecule imaging and bulk cleavage assays with purified coreTFIIH and XPG

    PMID:36477609 PMID:37076618

    Open questions at the time
    • Role of p62 during XPG-stimulated helicase switching not individually resolved
    • Complete reconstitution of dual incision with full kinetic characterization remains incomplete
  11. 2024 High

    STK19 was identified as a factor positioning TFIIH ahead of stalled RNA Pol II during transcription-coupled NER, with structural evidence that it bridges CSA, RPB1, and XPD to facilitate lesion verification.

    Evidence Cell-free TC-NER reconstitution in Xenopus egg extract, 1.9 Å cryo-EM structure, AlphaFold-guided mutagenesis

    PMID:39547228

    Open questions at the time
    • Whether STK19 kinase activity contributes to TFIIH regulation unknown
    • Validation in mammalian cell TC-NER needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The allosteric mechanism by which p62 binding to XPD regulates helicase activity, and how activator binding to p62 is transmitted to TFIIH enzymatic outputs, remain structurally and biochemically unresolved.
  • No reconstituted biochemical dissection of p62-specific allosteric regulation of XPD helicase kinetics
  • Structural basis for activator–p62 interaction at atomic resolution unknown
  • In vivo dynamics of p62 during the transcription-to-repair switch not measured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140223 general transcription initiation factor activity 4 GO:0003677 DNA binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3
Pathway
R-HSA-73894 DNA Repair 10 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1643685 Disease 2
Partners
CDK7MAT1UVSSAXPAXPBXPCXPDXPG
Complex memberships
TFIIH core complexTFIIH holoenzyme (core + CAK module)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 BTF2 (later renamed TFIIH), a general transcription factor containing the GTF2H1/p62 subunit, was purified from HeLa cells and shown to be absolutely required for formation of a functional transcription initiation complex; it binds RNA polymerase II and other general transcription factors (TFIID, BTF3, BTF4) in solution. Biochemical purification, in vitro transcription reconstitution, protein-protein interaction assays The Journal of biological chemistry High 1939143
1993 The 89 kDa subunit of BTF2/TFIIH (containing the GTF2H1/p62 subunit) was identified as the ERCC3/XPB helicase; the intact complex possesses ATP-dependent DNA helicase activity in addition to CTD kinase activity, demonstrating that TFIIH directly links transcription and nucleotide excision repair. Strand displacement helicase assay, amino acid sequence analysis of tryptic digest of purified BTF2 subunit Science High 8465201
1994 The GTF2H1/p62 subunit of TFIIH is the binding site for acidic transcriptional activation domains of VP16 and p53; point mutations in VP16 that reduce transactivation in vivo weaken binding to p62 of TFIIH and to the homologous TFB1 subunit of yeast factor b. Protein-protein interaction assays, GST pulldown, mutational analysis of VP16 activation domain, yeast two-hybrid Molecular and cellular biology High 7935417
1994 ERCC2/XPD was found to copurify with BTF2/TFIIH; antibodies to the p62 (GTF2H1) subunit of BTF2 immunoprecipitate ERCC2, establishing p62 as part of the core TFIIH complex that contains multiple DNA repair proteins. Antibody depletion of p62 from cell-free extracts abrogates NER activity. Co-immunoprecipitation, glycerol gradient sedimentation, antibody depletion, in vitro NER complementation assay The EMBO journal High 8194528
1994 TFIIH (containing GTF2H1/p62) has a dual role: it is required for basal transcription of class II genes and participates directly in DNA excision repair, complementing XPB/ERCC3, XPD/ERCC2, and XPC repair-deficient extracts. TFIIE negatively modulates TFIIH helicase activity through direct interaction with the ERCC3 subunit. In vitro transcription reconstitution, in vitro NER complementation with cell-free extracts, helicase inhibition assay Nature High 8152490
1994 The p62 subunit of BTF2/TFIIH and the ERCC3 (XPB) subunit both possess DNA-dependent ATPase activity; the ATPase resides in the p89/ERCC3 polypeptide. Wild-type but not ATPase-dead recombinant p89/ERCC3 supports helicase activity. The ATPase/helicase activity is pharmacologically and biochemically distinguishable from the CTD kinase activity within the same complex. In vitro ATPase assay with purified BTF2, recombinant wild-type and mutant p89/ERCC3, nucleotide competition and inhibitor studies The Journal of biological chemistry High 7511595
1994 TFIIH (containing GTF2H1/p62) has DNA-dependent ATPase activity; TFIIE stimulates both the ATPase and CTD kinase activities of TFIIH in a manner dependent on the stage of preinitiation complex assembly. Extensive RNA polymerase II CTD phosphorylation occurs in a TFIIE-dependent manner. In vitro ATPase and kinase assays with purified human TFIIH and TFIIE, preinitiation complex assembly on promoter DNA Nature High 8166891
1994 TFIIH containing the GTF2H1/p62 subunit directly participates in NER in vivo: antibody depletion and microinjection experiments demonstrate the p62 BTF2 subunit (and likely the entire complex) functions in excision repair. Expression of dominant-negative ATPase-dead ERCC3 abrogates both NER and transcription. In vivo microinjection NER assay, antibody depletion from cell-free extracts, dominant-negative ERCC3 expression The EMBO journal High 8157004
1995 Wild-type p53 binds TFIIH-associated repair factors XPD and XPB (subunits of the complex that also contains GTF2H1/p62) via its C-terminal domain, and inhibits XPD and XPB DNA helicase activities in vitro; mutant p53 (Arg273His) lacks this inhibitory function. Co-immunoprecipitation, in vitro helicase inhibition assay, UV repair assay in Li-Fraumeni cells Nature genetics High 7663514
1995 The CDK-activating kinase (CAK) complex, consisting of Cdk7 and cyclin H, is a stable component of purified human TFIIH (which contains GTF2H1/p62). Anti-cyclin H antibodies inhibit TFIIH-dependent transcription; both cyclin H and Cdk7 antibodies inhibit CTD phosphorylation within the preinitiation complex. Biochemical purification, co-immunoprecipitation with anti-cyclin H and anti-Cdk7 antibodies, in vitro transcription and kinase inhibition assays Nature High 7533895
1995 TFIIH preparations containing kinase-deficient MO15/CDK7 lack CTD kinase activity but are fully functional in both basal and activated transcription in vitro, demonstrating that CTD phosphorylation is not required for the transcriptional function of TFIIH (which contains GTF2H1/p62). In vitro transcription reconstitution with kinase-deficient TFIIH preparations Proceedings of the National Academy of Sciences of the United States of America High 7761469
1996 Tat stimulates HIV-1 transcription in vitro by interacting with a TFIIH-containing complex (which includes GTF2H1/p62) through its activation domain, stimulating TFIIH-mediated CTD phosphorylation and enhancing RNA polymerase II elongation processivity. In vitro transcription and kinase assay, co-immunoprecipitation of Tat with TFIIH Nature Medium 8934526
1996 VP16 (type IIB activator) and Tat (type IIA activator) differ in their interactions with TFIIH: the ability of activators to stimulate elongation (but not initiation only) correlates with their ability to bind TFIIH containing the GTF2H1/p62 subunit. Nuclear run-on assay, RNase protection, TFIIH binding assays with mutant activators Molecular and cellular biology Medium 8628270
2000 Electron microscopy of single particles of human TFIIH revealed it to be a ring-like structure (16×12.5×7.5 nm) from which a large protein domain protrudes. Immunolabeling localized p44 within the ring forming the base of the protruding density, which contains CDK7/cyclin H/MAT1; within the ring, p44 is flanked by XPB and XPD helicases. These results place GTF2H1/p62 within the ring architecture of TFIIH. Electron microscopy with single particle analysis, immunolabeling with subunit-specific antibodies, recombinant five-subunit core subcomplex assembly Cell High 11007478
2000 Ligand-dependent phosphorylation of estrogen receptor alpha at S118 by CDK7 within TFIIH requires an interaction of TFIIH with the AF2 domain of ERα; this interaction involves the p62 (GTF2H1) and XPD subunits of the core TFIIH. AF2 helix 12 integrity is required for productive TFIIH binding. In vitro CDK7 kinase assay, co-immunoprecipitation with anti-p62 and anti-XPD antibodies, mutational analysis of ERα AF2 Molecular cell High 10949034
2004 GTF2H5/TTDA (TFB5), the tenth subunit of TFIIH, was identified; mutations in this gene cause TTD-A, and its product regulates the overall cellular level of TFIIH. This identifies GTF2H1/p62 and the entire TFIIH complex as requiring GTF2H5 for stability. Microinjection of cDNA for complementation of TTD-A repair defect, mutation identification in TTD-A families, TFIIH co-purification assays Nature genetics High 15220921
2004 In Saccharomyces cerevisiae, the TFIIH kinase subunit Kin28 phosphorylates Mediator subunit Med4 at Thr-237 both in vitro and in vivo; Mediator dramatically enhances Kin28 CTD kinase activity, and this enhancement is specific to TFIIH kinase and requires only the TFIIK subcomplex (Kin28/Ccl1/Tfb3). This places TFIIH in a mutual regulatory relationship with Mediator. In vitro kinase assay with purified holo-TFIIH and Mediator, mass spectrometry phosphosite identification, in vivo phosphorylation confirmation by mutagenesis The Journal of biological chemistry High 15126497
2006 p8/TTD-A (GTF2H5), the tenth TFIIH subunit, specifically stimulates XPB ATPase activity together with XPC-hHR23B to trigger DNA opening during NER, and this opening is required for subsequent XPA recruitment to the damage site. p8 is dispensable for RNA synthesis and does not interfere with the CAK transcriptional function, although it interacts with XPD. In vitro ATPase stimulation assay, fluorescent antibody localization, NER reconstitution, RNA synthesis assay with p8-depleted or p8-overexpressing extracts Molecular cell High 16427011
2009 In fission yeast, the TFIIH-associated kinase Mcs6 (CDK7 homolog) and P-TEFb (Cdk9) coordinately regulate RNA Pol II CTD phosphorylation at a common target gene; TFIIH primes the CTD and promotes recruitment of P-TEFb/cap methyltransferase Pcm1, coupling elongation and capping of select pre-mRNAs. Mcs6 activity is both sufficient and necessary for Cdk9/Pcm1 complex recruitment. Chemical-genetic analog-sensitive kinase inhibition, chromatin immunoprecipitation, RNA analysis, in vitro CTD phosphorylation assay Molecular cell High 19328067
2010 XPD forms a TFIIH-independent complex (MMXD) with MMS19, MIP18, Ciao1, and ANT2. XPD, MMS19, and MIP18 localize to the mitotic spindle; siRNA knockdown of MMS19, MIP18, or XPD causes improper chromosome segregation and accumulation of nuclei with abnormal shapes. XP-D patient cells also show increased abnormal mitosis, suggesting a role for XPD outside of TFIIH. Co-immunoprecipitation, siRNA knockdown with mitotic phenotype quantification, immunofluorescence localization to mitotic spindle Molecular cell High 20797633
2014 XPD helicase activity (ATPase and DNA binding) is exclusively required for NER within TFIIH, but is dispensable for transcription initiation; XPD instead acts as a structural scaffold for TFIIH integrity during transcription. Mutations in the 4Fe-4S cluster domain of XPD abrogate NER without affecting transcriptional activity. p44-dependent activation of XPD is mediated by stimulation of its ATPase activity. In vitro helicase/ATPase assays, in vivo NER and transcription complementation assays with XPD mutants, comparative analysis of human and thermostable fungal XPD PLoS biology High 25268380
2015 TFIIH subunit mutations (in XPB, XPD, or GTF2H5/p8) associated with XP, XP/CS, or TTD disrupt specific transcription steps at the RARB2 promoter, including TFIIH complex recruitment, recruitment of NER factors during transcription, post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. Different variants cause distinct transcriptional deficiencies explaining phenotypic variability. ChIP at RARB2 promoter in patient cells, histone modification analysis, DNA break and demethylation assays, gene-loop analysis American journal of human genetics High 25620205
2017 Cryo-EM structures of the yeast PIC and PIC-Mediator complex reveal that TFIIH core subunit Ssl2 (XPB homolog) is positioned on downstream DNA by the E-bridge helix in TFIIE, consistent with TFIIE-stimulated DNA opening. The TFIIH kinase module subunit Tfb3 (MAT1) anchors kinase Kin28 (CDK7), which is mobile in PIC but preferentially located between Mediator hook and shoulder in PIC-Mediator. The p62 (GTF2H1) homolog is part of the ring structure. Cryo-electron microscopy at 4.7 Å (PIC) and 5.8 Å (PIC-Mediator) resolution Nature High 29088706
2017 CDK7 within human TFIIH (which contains GTF2H1/p62) phosphorylates the RNA Pol II CTD to regulate capping enzyme recruitment, promoter-proximal pausing, and termination. CDK7-phosphorylated CTD selectively binds capping enzymes and H3K4 methyltransferases SETD1A/B, and TFIIH-phosphorylated CTD directly stimulates SETD1A/B activity toward nucleosomes, providing a mechanistic basis for CDK7 regulation of H3K4me3 spreading. CDK7 analog-sensitive cell lines, ChIP-seq, mass spectrometry pull-down with phospho-CTD peptides, in vitro histone methyltransferase activity assay Cell reports High 28768201
2017 In Drosophila, the RNA-recognition motif protein Half pint (Hfp) represses dmyc transcription and cell growth through physical and genetic interaction with the XPB helicase subunit (Haywire/Hay) of TFIIH. Hfp binds the dmyc promoter in vivo, and loss of Hay abolishes normal levels of dmyc expression. ChIP at dmyc promoter, genetic epistasis (Hfp × hay double mutants), co-immunoprecipitation of Hfp and Hay, in vivo cell growth and cell cycle analysis Development Medium 20667914
2017 In nucleotide excision repair, both GGR initiation factor XPC and TCR initiation factor UVSSA recruit TFIIH via the pleckstrin homology (PH) domain of TFIIH subunit p62 (GTF2H1). UVSSA binds the basic groove of the p62 PH domain through a short acidic string (Phe408, Val411); mutation of these residues markedly diminishes TCR activity. This defines a common TFIIH recruitment mechanism for both NER subpathways. NMR structure of UVSSA-p62 PH domain complex, mutational binding analysis, TCR activity assay in UVSSA-deficient cells with mutant UVSSA reconstitution Nucleic acids research High 29069470
2019 Cryo-EM structure of the complete human TFIIH core complex at 3.7 Å resolution reveals how XPB recruitment by p52 depends on a pseudo-symmetric dimer of homologous domains in these two proteins. The structure reveals a function for p62 (GTF2H1) in the regulation of XPD: p62 contacts XPD and is proposed to influence XPD helicase activity; the structure also allows mapping of previously unresolved human disease mutations onto specific subunit interfaces. Phase-plate cryo-electron microscopy at 3.7 Å resolution of purified human TFIIH core complex eLife High 30860024
2019 Cryo-EM structure of an NER intermediate containing TFIIH and XPA shows that compared to its transcription conformation, TFIIH is rearranged such that XPB and XPD bind double- and single-stranded DNA respectively. XPA releases the inhibitory CAK kinase module from TFIIH, displaces a 'plug' element from the XPD DNA-binding pore, and together with XPG stimulates XPD helicase activity, explaining how TFIIH switches from a transcription to a repair factor. Cryo-electron microscopy of NER intermediate complex containing TFIIH and XPA Nature communications High 31253769
2019 TFIIE orchestrates CAK (kinase module) recruitment into the preinitiation complex through interactions between TFIIEα/TFIIEβ subunits and the TFIIH kinase module; RNA Pol II phosphorylation and DNA opening trigger release of CAK and TFIIEα from the promoter. This dissociation is blocked by ATP-γS or CDK7 inhibitor THZ1 but not by XPB inactivation. Core-TFIIH and TFIIEβ are subsequently removed as elongation factors are recruited. ChIP of TFIIH subunits at transcription start sites, co-immunoprecipitation, in vitro reconstituted transcription, CDK7 inhibitor treatment Nature communications High 31064989
2018 SWI/SNF ATPases BRM/SMARCA2 and BRG1/SMARCA4 promote expression of GTF2H1 (p62 subunit of TFIIH); inactivation of either ATPase downregulates GTF2H1, compromising TFIIH stability and function in both transcription and NER. Sensitivity of SWI/SNF-deficient cancer cells to UV irradiation and cisplatin depends on GTF2H1 levels, identifying GTF2H1 as a predictive marker of platinum sensitivity. BRM/BRG1 knockdown with GTF2H1 mRNA/protein measurement, TFIIH stability assay, NER assay (unscheduled DNA synthesis), UV/cisplatin sensitivity assay, GTF2H1 re-expression rescue Nature communications High 30287812
2020 Timely dissociation of DDB2 from UV-induced lesions is required for DNA damage handover to XPC and progression of NER; arrival of TFIIH (containing GTF2H1/p62) at the damage site promotes DDB2 dissociation and stabilizes the XPC-TFIIH damage verification complex. Live-cell imaging, FRAP, co-immunoprecipitation, ubiquitination assays, NER progression assays Nature communications High 32985517
2020 The Arch domain of XPD within TFIIH physically interacts with MAT1 (a CAK subunit); mutagenesis of the Arch-MAT1 interface identifies residues essential for NER activity (via XPD helicase regulation or XPD-XPG interaction) and for RNA Pol II CTD phosphorylation and RNA synthesis. MAT1 shields functionally important Arch domain residues, defining the Arch domain as a key mechanistic player within the XPD scaffold of TFIIH. Crystal structure of XPD Arch domain with MAT1, site-directed mutagenesis, in vitro NER and helicase assays, in vitro transcription assay Nature communications High 32245994
2023 Cryo-EM structures capture lesion recognition by human XPC and DNA lesion handoff from XPC to TFIIH core complex (Core7) and XPA. XPA, binding between XPB and XPD of TFIIH, kinks the DNA duplex and shifts XPC and the lesion by nearly a helical turn relative to Core7, positioning the lesion outside of TFIIH (as with RNA Pol II). XPB and XPD track the lesion-containing strand in opposite directions to push/pull it into XPD for verification. Cryo-electron microscopy of human XPC-Core7-XPA complexes on damaged DNA Nature High 37076618
2023 XPG binding to TFIIH core (coreTFIIH) stimulates coreTFIIH-dependent dsDNA unwinding 10-fold and XPG-dependent DNA cleavage up to 700-fold; XPG switches coreTFIIH from ssDNA translocation to dsDNA unwinding as a committed step. XPG incision activity is suppressed during coreTFIIH translocation but is licensed when coreTFIIH stalls at a lesion or ATP hydrolysis is blocked. At least 15 nt of 5'-ssDNA is required for efficient translocation and incision. Single-molecule imaging, bulk cleavage assays, simultaneous monitoring of ssDNA translocation and dsDNA unwinding rates with purified coreTFIIH and XPG Nucleic acids research High 36477609
2024 STK19 is required for transcription-coupled NER (TC-NER) in a cell-free Xenopus egg extract system. A 1.9 Å cryo-EM structure shows STK19 binds the TC-NER complex through CSA and RPB1 of RNA Pol II; AlphaFold modeling and mutational disruption of the STK19-XPD interface impairs cell-free repair, suggesting STK19 positions TFIIH ahead of stalled RNA Pol II for lesion verification. Cell-free TC-NER reconstitution in Xenopus egg extract, 1.9 Å cryo-EM structure, AlphaFold interface prediction with mutational validation Cell High 39547228

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
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
2014 An atlas of genetic influences on human blood metabolites. Nature genetics 1209 24816252
1999 Quality control by DNA repair. Science (New York, N.Y.) 1187 10583946
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
2009 Monitoring autophagic degradation of p62/SQSTM1. Methods in enzymology 991 19200883
2013 Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Molecular cell 969 24011591
2009 p62 at the crossroads of autophagy, apoptosis, and cancer. Cell 938 19524504
2020 A reference map of the human binary protein interactome. Nature 849 32296183
1996 The general transcription factors of RNA polymerase II. Genes & development 849 8946909
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2001 Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 A resolution. Science (New York, N.Y.) 740 11313499
1993 DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. Science (New York, N.Y.) 725 8465201
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
2015 p62/SQSTM1 functions as a signaling hub and an autophagy adaptor. The FEBS journal 669 26432171
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Genome-scale RNAi screen for host factors required for HIV replication. Cell host & microbe 627 18976975
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2015 p62 links autophagy and Nrf2 signaling. Free radical biology & medicine 535 26117325
1995 p53 modulation of TFIIH-associated nucleotide excision repair activity. Nature genetics 520 7663514
2010 Physiological significance of selective degradation of p62 by autophagy. FEBS letters 445 20153326
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1994 Dual role of TFIIH in DNA excision repair and in transcription by RNA polymerase II. Nature 436 8152490
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
1995 Cdk-activating kinase complex is a component of human transcription factor TFIIH. Nature 395 7533895
2018 DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell 379 29656893
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
1994 The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. The EMBO journal 342 8194528
1994 Binding of basal transcription factor TFIIH to the acidic activation domains of VP16 and p53. Molecular and cellular biology 328 7935417
2018 p62 filaments capture and present ubiquitinated cargos for autophagy. The EMBO journal 297 29343546
2006 Signal integration and diversification through the p62 scaffold protein. Trends in biochemical sciences 278 17174552
2006 p62/SQSTM1: a missing link between protein aggregates and the autophagy machinery. Autophagy 266 16874037
2004 A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A. Nature genetics 263 15220921
2012 p62/SQSTM1/A170: physiology and pathology. Pharmacological research 254 22841931
2012 TFIIH: when transcription met DNA repair. Nature reviews. Molecular cell biology 247 22572993
1996 Enhanced processivity of RNA polymerase II triggered by Tat-induced phosphorylation of its carboxy-terminal domain. Nature 245 8934526
1996 Three functional classes of transcriptional activation domain. Molecular and cellular biology 244 8628270
1998 A human RNA polymerase II complex containing factors that modify chromatin structure. Molecular and cellular biology 242 9710619
2000 Activation of estrogen receptor alpha by S118 phosphorylation involves a ligand-dependent interaction with TFIIH and participation of CDK7. Molecular cell 241 10949034
2018 p62/SQSTM1 - steering the cell through health and disease. Journal of cell science 232 30397181
2010 Selective degradation of p62 by autophagy. Seminars in immunopathology 212 20814791
2017 Structures of transcription pre-initiation complex with TFIIH and Mediator. Nature 208 29088706
2018 p62/SQSTM1: 'Jack of all trades' in health and cancer. The FEBS journal 206 30499183
2018 Autophagic Regulation of p62 is Critical for Cancer Therapy. International journal of molecular sciences 205 29738493
2016 TRIM21 Ubiquitylates SQSTM1/p62 and Suppresses Protein Sequestration to Regulate Redox Homeostasis. Molecular cell 191 26942676
1991 Purification and interaction properties of the human RNA polymerase B(II) general transcription factor BTF2. The Journal of biological chemistry 173 1939143
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