Affinage

ERCC3

General transcription and DNA repair factor IIH helicase/translocase subunit XPB · UniProt P19447

Length
782 aa
Mass
89.3 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC3 (XPB) is the 3′→5′ DNA helicase and ATPase subunit of the general transcription factor TFIIH, serving dual essential roles in RNA polymerase II transcription initiation and nucleotide excision repair (NER) (PMID:8465201, PMID:2167179). Its ATPase activity, stimulated by the p52/p8 subcomplex independently of DNA, drives promoter melting to form the open complex during transcription initiation, while its helicase activity is separately required for promoter escape and productive early elongation; these functions are mechanistically dissociable from its NER role, in which ATPase-driven DNA opening around lesions enables recruitment of downstream incision factors XPA, XPG, and XPF-ERCC1 (PMID:15937491, PMID:17466626, PMID:10428772, PMID:17509950). Phosphorylation of Ser751 by CDK7 selectively inhibits the 5′ NER incision without affecting transcription, while CDK7-mediated phosphorylation of Ser90 triggers SCF^FBXL18-dependent ubiquitination and proteasomal degradation of XPB (PMID:15549133, PMID:30762924). XPB is covalently targeted at Cys342 by triptolide, which blocks its ATPase activity and thereby inhibits global transcription, and loss-of-function mutations in ERCC3 cause xeroderma pigmentosum complementation group B, a disorder of defective NER, with additional impairment of p53-dependent apoptosis (PMID:21278739, PMID:25504624, PMID:2167179, PMID:8675009).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 High

    Cloning of ERCC3 revealed it encodes a putative helicase that corrects the NER defect in XP complementation group B, establishing the molecular identity of the XP-B disease gene and linking it to DNA repair.

    Evidence cDNA cloning with sequence analysis and transfection complementation in UV-sensitive rodent and human XP-B cells

    PMID:2111438 PMID:2167179

    Open questions at the time
    • Enzymatic activity not yet demonstrated directly
    • Role in transcription unknown at this point
  2. 1992 High

    Cell-free NER assays and yeast genetics established that ERCC3/Ssl2 is directly required for the incision reaction in NER and is also essential for general RNA polymerase II transcription, revealing its dual function.

    Evidence In vitro NER complementation with repair-deficient extracts; yeast SSL2 conditional mutants showing decreased poly(A)+ RNA synthesis

    PMID:1318786 PMID:1551896 PMID:7693549

    Open questions at the time
    • Whether ERCC3 acts in transcription as part of a larger complex was unknown
    • Mechanism of action in both processes unresolved
  3. 1993 High

    Identification of ERCC3 as the p89 subunit of the basal transcription factor BTF2/TFIIH unified DNA repair and transcription into a single multi-subunit complex, explaining the dual phenotype.

    Evidence Tryptic peptide sequencing of the 89 kDa BTF2 subunit matched ERCC3; helicase assay on purified BTF2

    PMID:8465201

    Open questions at the time
    • Which enzymatic activity (ATPase vs. helicase) drives each function was unclear
    • How TFIIH subunits regulate XPB activity was unknown
  4. 1994 High

    Systematic mutagenesis and reconstitution demonstrated that XPB possesses intrinsic 3′→5′ helicase and DNA-dependent ATPase activities, that its ATPase motif is essential for both NER and transcription in vivo, and that ERCC2/XPD copurifies with XPB within TFIIH.

    Evidence Recombinant XPB helicase assay, ATPase assay with motif mutants, dominant-negative K436R mutant microinjection, co-IP of ERCC2 with ERCC3

    PMID:7511595 PMID:7937133 PMID:8157004 PMID:8194528 PMID:8196650

    Open questions at the time
    • Whether ATPase and helicase are separable for each function was not resolved
    • How TFIIH opens promoter DNA mechanistically was unknown
  5. 1996 High

    XPB was placed in the p53-dependent apoptosis pathway: XP-B patient fibroblasts failed to undergo p53-induced apoptosis, which was rescued by wild-type XPB gene transfer, establishing a role beyond repair and basal transcription.

    Evidence Microinjection of p53 into XP-B patient and normal fibroblasts, genetic rescue, apoptosis quantification

    PMID:8675009

    Open questions at the time
    • Molecular mechanism linking XPB to apoptotic signaling unresolved
    • Whether this reflects transcriptional requirement for pro-apoptotic genes or a distinct function was unclear
  6. 1997 High

    Discovery of a direct XPB–SUG1 (26S proteasome subunit) interaction via multiple methods linked TFIIH to proteasome function and transcription-coupled chromatin dynamics.

    Evidence Yeast two-hybrid, baculovirus co-expression, co-IP from fibroblasts; SUG1 overexpression causes transcription arrest

    PMID:9173976

    Open questions at the time
    • Physiological relevance of XPB–proteasome interaction not fully defined
    • Whether SUG1 regulates XPB stability or activity was unknown
  7. 1999 High

    Full reconstitution of TFIIH from recombinant subunits proved that XPB helicase is absolutely required for promoter opening and that its helicase activity separately promotes promoter escape, while XPD helicase is dispensable for open complex formation.

    Evidence Baculovirus-reconstituted TFIIH with helicase-dead mutants in in vitro transcription; patient-derived TFIIH showing bypass of defect by pre-opened bubble substrates

    PMID:10024882 PMID:10064601 PMID:10428772

    Open questions at the time
    • Whether promoter opening requires strand separation (helicase) or conformational remodeling (ATPase) was not distinguished
  8. 2002 High

    The p52 subunit was identified as the TFIIH anchor for XPB, with its C-terminus essential for promoter opening, NER, and stimulation of XPB activity, defining an intra-complex regulatory axis.

    Evidence Reconstituted TFIIH with p52 domain deletions, NER and transcription assays

    PMID:12080057

    Open questions at the time
    • p8 contribution to XPB activation not yet characterized
    • Structural basis of p52–XPB interaction unknown
  9. 2004 High

    Phosphorylation of XPB at Ser751 was shown to selectively inhibit NER (specifically the 5′ incision by ERCC1-XPF) without affecting transcription, establishing a post-translational switch that uncouples the two TFIIH functions.

    Evidence In vivo phosphorylation mapping, microinjection of phospho-mutant XPB into XP-B cells, in vitro dual-incision NER assay

    PMID:15549133

    Open questions at the time
    • Identity of the kinase phosphorylating Ser751 was not established in this study
    • Structural basis for how pSer751 blocks XPF incision was unknown
  10. 2005 High

    Separation-of-function analysis distinguished XPB ATPase from helicase activity: ATPase drives promoter melting via conformational remodeling (not strand separation), while helicase activity is required for promoter escape, resolving a longstanding mechanistic question.

    Evidence In vitro transcription with XPB ATPase-only and helicase-dead mutants

    PMID:15937491

    Open questions at the time
    • Whether this ATPase-only mechanism also applies to NER DNA opening was untested
  11. 2006 High

    The crystal structure of an archaeal XPB homolog revealed the domain architecture (DRD, RED motif, ThM, two RecA-like domains) and showed the DRD confers specificity for damaged DNA, providing the first structural framework for XPB function.

    Evidence X-ray crystallography of AfXPB; RED motif mutagenesis reducing helicase activity; DRD binding to CPD and 6-4PP substrates

    PMID:16600867

    Open questions at the time
    • Human XPB full-length structure not available
    • How DRD functions within the TFIIH holocomplex context was unknown
  12. 2007 High

    ATPase (not helicase) activity of XPB was shown to be the critical enzymatic activity for NER DNA opening, with p52 stimulating this ATPase; XPB was also shown to be required for downstream recruitment of NER incision factors to damage sites.

    Evidence NER dual-incision assay with helicase-motif mutants retaining NER; p52-XPB interaction mapping; local UV irradiation with factor recruitment imaging in XP-B cells

    PMID:17466626 PMID:17509950

    Open questions at the time
    • How XPB ATPase generates the NER bubble without strand separation activity was not structurally resolved
  13. 2011 High

    Triptolide was identified as a covalent inhibitor of XPB ATPase activity, providing a chemical tool that blocks both transcription and NER by targeting XPB directly.

    Evidence Affinity labeling and ATPase inhibition assay with triptolide; knockdown/rescue confirming XPB as target

    PMID:21278739

    Open questions at the time
    • Exact binding site on XPB not yet mapped
    • Selectivity profile against other ATPases not fully characterized
  14. 2014 High

    Cys342 was identified as the specific covalent modification site of triptolide on XPB; CRISPR knock-in of C342T conferred complete triptolide resistance, validating the target and enabling structure-activity pharmacology.

    Evidence Mass spectrometry, C342T mutagenesis, CRISPR/Cas9 knock-in in HEK293T cells

    PMID:25504624

    Open questions at the time
    • Whether Cys342 modification alone accounts for all triptolide cellular effects was not fully excluded
  15. 2019 High

    The degradation pathway for XPB was delineated: CDK7 phosphorylates Ser90, which is recognized by the E3 ligase SCF^FBXL18 for polyubiquitination and proteasomal degradation, providing the molecular mechanism for spironolactone-induced XPB turnover.

    Evidence siRNA screen identifying FBXL18, co-IP, ubiquitination assay, Ser90 mutagenesis, CDK7 inhibitor experiments

    PMID:30762924

    Open questions at the time
    • Whether this degradation pathway operates under physiological conditions beyond drug treatment was not established
    • Signals that normally trigger Ser90 phosphorylation are unknown
  16. 2020 High

    The p52/p8 heterodimer was established as the master activator of XPB ATPase, functioning independently of DNA; within assembled core TFIIH, XPB acts as a processive translocase whose processivity is enhanced by XPA, integrating subunit-level regulation of XPB enzymatic output.

    Evidence Crystal structure of p52/p8, cryo-EM-guided mutagenesis, quantitative ATPase and translocase assays

    PMID:33196848

    Open questions at the time
    • How translocase activity relates to bubble opening in the context of a full NER pre-incision complex is not resolved
    • Regulation of p52/p8 activation upon DNA damage is unclear
  17. 2024 High

    A monofunctional covalent degrader (ZL-12A) targeting XPB Cys342 was shown to induce proteasomal degradation of XPB, unlike triptolide at the same site, revealing that covalent modification chemistry at Cys342 determines whether XPB is degraded or merely inhibited.

    Evidence Cysteine-directed ABPP, competitive pulldown, western blotting for degradation kinetics, cross-antagonism with triptolide

    PMID:38569115

    Open questions at the time
    • Structural basis for why different Cys342 adducts trigger or prevent degradation is unknown
    • In vivo therapeutic utility not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural mechanism by which XPB ATPase-driven conformational change melts promoter DNA within the full preinitiation complex, how the DRD damage verification domain operates within human TFIIH during NER, and what physiological signals regulate XPB degradation through the CDK7–FBXL18 axis.
  • No full-length human XPB structure in the context of the preinitiation complex with melted DNA
  • DRD function not validated in human NER
  • Physiological triggers of CDK7-Ser90 phosphorylation leading to XPB degradation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 6 GO:0003677 DNA binding 4 GO:0016787 hydrolase activity 4
Localization
GO:0005634 nucleus 1
Pathway
R-HSA-73894 DNA Repair 8 R-HSA-74160 Gene expression (Transcription) 7 GO:0005634 nucleus 1 R-HSA-392499 Metabolism of proteins 1 R-HSA-5357801 Programmed Cell Death 1
Partners
CDK7ERCC2GTF2H1GTF2H4PSMC5TP53XPA
Complex memberships
TFIIH

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 ERCC3 encodes a presumed DNA helicase containing seven conserved helicase motifs from two superfamilies, and specifically corrects the nucleotide excision repair (NER) defect of XP complementation group B rodent mutants; a splice acceptor mutation in the last intron causes a frameshift in the C-terminus, inactivating the protein in the XP-B patient. cDNA cloning, sequence analysis, transfection complementation assay in UV-sensitive rodent mutants Cell High 2167179
1990 ERCC3 corrects the NER defect in XP group B cells and is required for an early incision step in the excision repair pathway; the ERCC3 cDNA in an expression vector virtually completely corrects UV sensitivity and unscheduled DNA synthesis in complementation group 3 rodent mutants. cDNA transfection to UV-sensitive CHO cells (group 3), UV survival and UDS assay Molecular and cellular biology High 2111438
1993 The ERCC3 gene product (p89 subunit) is a component of the basal transcription factor BTF2/TFIIH, which possesses an ATP-dependent DNA helicase activity required for class II gene transcription, demonstrating that transcription and NER share the ERCC3-containing TFIIH complex. Strand displacement helicase assay on purified BTF2, tryptic digest amino acid sequencing of the 89 kDa BTF2 subunit identifying ERCC3 Science High 8465201
1994 ERCC3/XPB is directly implicated in nucleotide excision repair as part of the BTF2/TFIIH complex; antibody depletion of p62 (and likely the entire complex) abrogates NER in vitro; a dominant-negative K436R ERCC3 mutant (ATPase/helicase dead) completely abrogates both NER and transcription in vivo and induces chromatin collapse. In vitro NER cell-free extract assay, microinjection of antibody/dominant-negative mutant, in vivo NER assay The EMBO journal High 8157004
1994 Purified BTF2/TFIIH has a DNA-dependent ATPase activity that resides in the p89/ERCC3 subunit; recombinant wild-type but not ATPase-motif mutant ERCC3 shows this activity, and the ATPase is mechanistically linked to the helicase. In vitro ATPase assay, recombinant wild-type and mutant p89/ERCC3, inhibitor studies The Journal of biological chemistry High 7511595
1994 ERCC2 (XPD) is a component of BTF2/TFIIH and co-purifies with ERCC3; antibodies against ERCC3 (p89) immunoprecipitate ERCC2, and salt-dissociated ERCC2 re-addition enhances BTF2 transcription activity, establishing ERCC2 and ERCC3 as repair proteins within the TFIIH transcription complex. Co-immunoprecipitation, glycerol gradient sedimentation, immunoaffinity, in vitro transcription reconstitution The EMBO journal High 8194528
1994 Hepatitis B virus X protein (HBX) forms a complex with p53 and inhibits the in vitro association of p53 with ERCC3, thereby inhibiting p53-mediated transcriptional activation. In vitro co-immunoprecipitation/pulldown, in vivo transcription reporter assay Proceedings of the National Academy of Sciences of the United States of America Medium 8134379
1994 Mutational analysis of ERCC3 shows that the invariant lysine in ATPase helicase domain I, helicase domains II–VI deletions, and the helix-turn-helix DNA-binding motif deletion all abolish repair complementation; the C-terminal exon is a distinct determinant of DNA repair function; epitope-tagged ERCC3 accumulates in the nucleus. Site-directed mutagenesis, deletion analysis, transfection complementation assay in UV-sensitive rodent cells, nuclear localization by immunofluorescence Molecular and cellular biology High 8196650
1994 Recombinant XPB/ERCC3 produced in baculovirus-infected insect cells possesses intrinsic DNA helicase activity, demonstrating that the helicase activity is an intrinsic property of the ERCC3 protein itself. Baculovirus expression, protein purification, in vitro helicase assay Nucleic acids research High 7937133
1994 Yeast RAD25 (SSL2/ERCC3 homolog) has ssDNA-dependent ATPase and 3'→5' DNA helicase activities; RAD25-depleted extract shows a thermolabile transcription defect corrected by RAD25 protein; a DNA repair-defective rad25799am allele retains RNA pol II transcription function, showing the repair and transcription activities are separable; an ATPase motif mutation (Arg-392) abolishes RNA pol II transcription. Protein purification, in vitro ATPase/helicase assay, temperature-sensitive mutant extract complementation, RNA pol II transcription assay Nature High 8202161
1996 XPB (ERCC3) is a component of the p53-mediated apoptosis pathway; primary fibroblasts from XP-B patients (deficient in XPB) have a deficiency in p53-induced apoptosis that can be rescued by transfer of the wild-type XPB gene; XPB acts downstream of p53 but upstream of ICE/Ich-L proteases in the apoptotic pathway. Microinjection of p53 expression vector into primary normal and XP patient fibroblasts, retroviral infection, genetic rescue with wild-type XPB gene, apoptosis assay Genes & development High 8675009
1996 The XPB subunit (ERCC3) of TFIIH harbors a 3'→5' DNA helicase activity; a frameshift mutation in XP11BE patient reduces this helicase and DNA-dependent ATPase activity, causing severe NER defect and decreased basal in vitro transcription. Isolation of TFIIH from patient cells, helicase and ATPase assays, in vitro transcription, recombinant mutant protein analysis The Journal of biological chemistry High 8663148
1997 XPB directly interacts with SUG1, a subunit of the 26S proteasome; this interaction is validated by yeast two-hybrid, baculovirus co-expression, and co-purification from fibroblasts; overexpression of SUG1 arrests transcription and causes chromatin collapse in vivo; a patient-derived XPB mutation diminishes this interaction. Yeast two-hybrid, baculovirus co-expression, co-purification/co-immunoprecipitation from fibroblasts, in vivo transcription arrest assay Nucleic acids research High 9173976
1999 Reconstituted TFIIH from recombinant baculovirus subunits shows that XPB helicase activity is absolutely required for RNA pol II promoter opening during transcription, while XPD helicase is dispensable but stimulates transcription and anchors the CAK complex to TFIIH; CDK7 can phosphorylate the CTD of RNA pol II without promoter opening. Baculovirus reconstitution of TFIIH from recombinant subunits, helicase-dead mutants, in vitro transcription assay Molecular cell High 10024882
1999 Mutations in XPB from XP-B/CS patient cells decrease TFIIH transcriptional activity by preventing promoter opening; the transcription defect is circumvented by artificial bubble opening; XPB mutations decrease open complex formation, establishing XPB ATPase/helicase as essential for promoter melting. Immunopurification of TFIIH from patient cell extracts, in vitro transcription, restriction enzyme accessibility (bubble assay), western blot and enzymatic assays The EMBO journal High 10064601
1999 XPB DNA helicase is primarily responsible for preventing premature arrest of early elongating RNA pol II complexes during promoter escape, establishing its role in this post-initiation step. In vitro transcription with TFIIH mutants (helicase and kinase dead) in a minimal reconstituted system with purified factors The Journal of biological chemistry High 10428772
2002 The p52 subunit of TFIIH physically interacts with XPB and anchors it within TFIIH; deletion of the C-terminal region of p52 dramatically reduces TFIIH NER and transcription activities and prevents promoter opening, without affecting other TFIIH enzymatic activities. Reconstituted in vitro transcription/NER with recombinant TFIIH, domain mapping of p52-XPB interaction The Journal of biological chemistry High 12080057
2002 Hepatitis C virus NS5A protein inhibits p53-ERCC3 complex formation (shown by co-immunoprecipitation and pulldown) and represses p53-mediated transcription, linking viral disruption of p53-ERCC3 interaction to transcriptional impairment. In vivo co-immunoprecipitation, in vitro pulldown, transcription reporter assay Biochimica et biophysica acta Medium 12379483
2002 ERCC3 helicase activity of TFIIH plays a regulatory role in promoter escape during activated transcription, stimulating productive elongation during synthesis of the first ~10 nucleotides of RNA; this activity is separable from ERCC2 helicase and CDK7 kinase contributions. In vitro transcription assay with ERCC3 helicase-deficient TFIIH, abortive/productive initiation analysis Proceedings of the National Academy of Sciences of the United States of America High 11818577
2003 ERCC3 helicase activity of TFIIH alleviates PC4-mediated transcriptional repression via beta-gamma bond hydrolysis of ATP, relieving topological constraint at the promoter; ERCC2 helicase and CDK7 kinase are not required for this alleviation. In vitro transcription assay with recombinant TFIIH, PC4, and mutant subunits; ATP analog competition The Journal of biological chemistry High 12590132
2004 Serine 751 (S751) of XPB is phosphorylated in vivo; this phosphorylation specifically inhibits NER (the 5' incision by ERCC1-XPF endonuclease) without affecting TFIIH-dependent transcription; dephosphorylation or S751A mutation restores NER; phosphomimetic S751E mutant cannot correct XP-B cells. In vivo phosphorylation analysis, microinjection of phospho/dephospho/mutant XPB into XP-B cells, in vitro NER incision assay, dual incision assay The EMBO journal High 15549133
2005 XPB ATPase activity (not helicase activity per se) drives RNA pol II promoter opening; XPB helicase activity is required for promoter escape but not for open complex formation, suggesting an ATP-driven conformational change mechanism analogous to bacterial sigma54-dependent transcription. Characterization of XPB helicase and ATPase mutants in promoter opening and escape assays in vitro Nature structural & molecular biology High 15937491
2006 Crystal structure of an archaeal XPB homolog (AfXPB) reveals two RecA-like helicase domains, a DNA damage recognition domain (DRD), a RED motif, and a flexible thumb motif (ThM); RED motif mutations dramatically reduce helicase activity; the DRD confers substrate specificity for damaged DNA (CPD, 6-4 photoproducts), implying a damage verification role. X-ray crystallography, site-directed mutagenesis of RED motif, helicase assay with damaged/undamaged DNA substrates Molecular cell High 16600867
2007 The p52 subunit of TFIIH interacts with XPB and stimulates its ATPase activity; XP-B patient mutation F99S weakens the p52-XPB interaction and reduces ATPase stimulation, explaining defective damaged-DNA opening; mutations in XPB helicase motifs III and VI that abolish helicase activity preserve NER function, indicating that XPB ATPase (not helicase) activity drives NER DNA opening. Co-immunoprecipitation, in vitro ATPase assay with wild-type and mutant XPB, NER dual incision assay with motif mutants Molecular cell High 17466626
2007 XPB is required for recruitment of NER proteins (XPA, XPG, XPF) to UV damage sites; XPC is recruited independently of XPB and acts upstream; XPF recruitment specifically requires functional XPB and is absent immediately after UV in XP-B cells regardless of mutation type. Local UV irradiation through micropore filters, fluorescent antibody labeling of NER factors in XP-B patient and normal cells, time-course imaging DNA repair High 17509950
2011 Triptolide covalently binds to human XPB (ERCC3), a subunit of TFIIH, and inhibits its DNA-dependent ATPase activity, thereby blocking RNA polymerase II-mediated transcription and likely NER. Chemical biology/affinity labeling, in vitro ATPase assay, RNA pol II transcription assay, knockdown/rescue experiments Nature chemical biology High 21278739
2012 Yeast Tfb6 (a newly identified 11th subunit of TFIIH) dissociates from TFIIH as a heterodimer with the Ssl2/XPB subunit after transcription initiation, but does not dissociate Ssl2 from assembled preinitiation complexes, indicating dynamic regulation of Ssl2/XPB engagement. Biochemical purification of TFIIH, identification of Tfb6 subunit, complex dissociation assay, preinitiation complex assembly assay Proceedings of the National Academy of Sciences of the United States of America High 22411836
2013 Crystal structure of the C-terminal half of human XPB (residues 494–782) at 1.8 Å reveals HD2 and a C-terminal extension structurally similar to RIG-I, providing a model for XPF-XPB-DNA interaction during 5' NER incision; the XP11BE frameshift mutation reduces XPB solubility and lowers intracellular TFIIH levels, impairing both repair and transcription. X-ray crystallography, western blotting of patient cell extracts, solubility assay of mutant protein Acta crystallographica. Section D, Biological crystallography High 23385459
2014 Triptolide covalently modifies Cys342 of XPB via cleavage of the 12,13-epoxide; mutation of Cys342 to threonine confers resistance to triptolide, and replacement of endogenous XPB with Cys342Thr in HEK293T cells renders them completely resistant, validating XPB as the physiologically relevant triptolide target. Mass spectrometry identification of modified cysteine, site-directed mutagenesis, CRISPR/Cas9 knock-in of Cys342Thr, cellular triptolide resistance assay Angewandte Chemie (International ed. in English) High 25504624
2014 XPB binds G4 DNA motifs genome-wide (ChIP-Seq) and biochemical analysis shows XPB binds G4 DNA; XPB and XPD are enriched near transcription start sites at 20% of genes, especially highly transcribed genes, linking TFIIH helicases to G-quadruplex resolution during transcription. ChIP-Seq in human cells, biochemical G4 DNA binding assay Nature chemical biology Medium 24609361
2018 Spironolactone induces proteasome-dependent degradation of XPB, suppressing NF-κB and AP-1 inflammatory signalling in an MR-independent manner; proteasome inhibition or XPB overexpression prevents spironolactone-mediated transcription suppression; XPB degradation is associated with low basal RNAPII occupancy at target genes. Reporter assay, proteasome inhibitor rescue, siRNA knockdown, chromatin immunoprecipitation, XPB overexpression Cardiovascular research High 29036418
2019 Spironolactone-induced proteasomal degradation of XPB requires CDK7 kinase activity and the SCFFBXL18 E3 ubiquitin ligase; CDK7 phosphorylates XPB at Ser90, which is recognized by FBXL18 for polyubiquitination and proteasomal degradation. siRNA library screen, co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (Ser90), CDK7 inhibitor experiments Genes to cells : devoted to molecular & cellular mechanisms High 30762924
2020 XPB plays a critical role in HIV-1 transcription; spironolactone-induced XPB degradation reduces RNAPII recruitment to the HIV-1 genome and suppresses HIV transcription; shRNA knockdown of XPB confirms XPB degradation as the mechanism of action. shRNA knockdown of XPB, RNAPII ChIP, HIV transcription and latency reactivation assays Journal of virology High 33239456
2020 p52/p8 subunit interaction with XPB acts as the master regulator of its ATPase activity: p52/p8 activates XPB's ATPase independently of DNA but dominates the maximum activation when both DNA and p52/p8 are present; XPB only acts as a translocase within complete core TFIIH context; XPA increases processivity of XPB translocase without altering its ATPase rate. Crystal structure of p52/p8 complex, cryo-EM-guided mutagenesis, in vitro ATPase assay, translocase assay Nucleic acids research High 33196848
2024 Covalent modification of ERCC3/XPB at Cys342 by the spirocycle acrylamide compound ZL-12A promotes proteasomal degradation of ERCC3 (acting as a monofunctional degrader), whereas triptolide targeting the same Cys342 does not cause ERCC3 degradation; spironolactone also reacts with ERCC3_C342; ZL-12A and triptolide cross-antagonize each other's protein degradation profiles. Cysteine-directed ABPP, competitive pulldown, western blotting for ERCC3 degradation, cross-antagonism experiments Journal of the American Chemical Society High 38569115
1992 SSL2 (RAD25), the yeast homolog of ERCC3, encodes an essential 95 kDa ATP-dependent helicase; an SSL2 allele resembling the defective ERCC3 gene confers UV hypersensitivity; suppression of a HIS4 stem-loop translation block by SSL2 indicates a role in gene expression distinct from UV repair. Genetic complementation, UV sensitivity assay, sequence homology, suppressor screen Cell High 1318786
1993 Loss of RAD25 (Ssl2/XPB yeast homolog) function causes a large decrease in poly(A)+ RNA synthesis and inhibits transcription of a broad set of RNA pol II genes, establishing a general requirement for RAD25/XPB in RNA polymerase II transcription. Temperature-sensitive lethal rad25 mutant, Northern blot analysis of multiple yeast genes at non-permissive temperature Genes & development High 7693549
1996 Reconstituted yeast TFIIH (including Rad25/XPB) and purified Rad3 and Rad25 are both required for the incision step of NER in vitro; helicase-dead rad25-R392 mutant severely diminishes NER incision, indicating that Rad25/XPB DNA helicase function is required for the incision of damaged DNA. In vitro NER reconstitution with purified yeast proteins, incision assay, helicase-dead mutant protein The Journal of biological chemistry High 8631896
2011 Ssl2 (XPB yeast homolog) interacts with TFIIB and affects transcription start site selection and gene looping; an ssl2 allele (H508R in the DEVH helicase domain) suppresses TFIIB E62K defects in start site selection and gene looping, defining a functional TFIIB–Ssl2 interaction. Genetic suppressor screen, chromatin immunoprecipitation (ChIP) at promoter and terminator regions, transcription start site mapping The Journal of biological chemistry High 22081613
1992 Cell extracts from rodent XP complementation group 3 (ERCC3-deficient) cells are defective in in vitro NER; mixing with group 1 extracts restores NER; human XP-B cell extracts cannot complement group 3 extracts, confirming identity of ERCC3 with XP-B gene and establishing that ERCC3 is directly required for the incision reaction. Cell-free in vitro NER complementation assay using extracts from repair-deficient cell lines The Journal of biological chemistry High 1551896

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 DNA repair helicase: a component of BTF2 (TFIIH) basic transcription factor. Science (New York, N.Y.) 725 8465201
1994 Hepatitis B virus X protein inhibits p53 sequence-specific DNA binding, transcriptional activity, and association with transcription factor ERCC3. Proceedings of the National Academy of Sciences of the United States of America 629 8134379
1990 A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders xeroderma pigmentosum and Cockayne's syndrome. Cell 438 2167179
2011 XPB, a subunit of TFIIH, is a target of the natural product triptolide. Nature chemical biology 413 21278739
1994 The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. The EMBO journal 342 8194528
1996 The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes & development 302 8675009
1999 Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7. Molecular cell 260 10024882
2007 Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair. Molecular cell 227 17466626
1994 RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription. Nature 179 8202161
1991 Purification and interaction properties of the human RNA polymerase B(II) general transcription factor BTF2. The Journal of biological chemistry 173 1939143
2014 G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD. Nature chemical biology 166 24609361
1999 Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO journal 161 10064601
1997 A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. American journal of human genetics 141 9012405
2011 XPB and XPD helicases in TFIIH orchestrate DNA duplex opening and damage verification to coordinate repair with transcription and cell cycle via CAK kinase. DNA repair 140 21571596
1992 SSL2, a suppressor of a stem-loop mutation in the HIS4 leader encodes the yeast homolog of human ERCC-3. Cell 136 1318786
2006 Conserved XPB core structure and motifs for DNA unwinding: implications for pathway selection of transcription or excision repair. Molecular cell 125 16600867
1994 Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3. American journal of human genetics 123 8304337
1992 RAD25 (SSL2), the yeast homolog of the human xeroderma pigmentosum group B DNA repair gene, is essential for viability. Proceedings of the National Academy of Sciences of the United States of America 120 1333609
1990 Molecular cloning and biological characterization of the human excision repair gene ERCC-3. Molecular and cellular biology 120 2111438
1992 A Drosophila model for xeroderma pigmentosum and Cockayne's syndrome: haywire encodes the fly homolog of ERCC3, a human excision repair gene. Cell 115 1458540
1994 Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH). The EMBO journal 111 8157004
1994 p44 and p34 subunits of the BTF2/TFIIH transcription factor have homologies with SSL1, a yeast protein involved in DNA repair. The EMBO journal 107 8194529
1992 Cloning of the 62-kilodalton component of basic transcription factor BTF2. Science (New York, N.Y.) 106 1529339
2006 Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Human mutation 104 16947863
1993 The Saccharomyces cerevisiae DNA repair gene RAD25 is required for transcription by RNA polymerase II. Genes & development 79 7693549
1999 A role for the TFIIH XPB DNA helicase in promoter escape by RNA polymerase II. The Journal of biological chemistry 77 10428772
2014 Covalent modification of a cysteine residue in the XPB subunit of the general transcription factor TFIIH through single epoxide cleavage of the transcription inhibitor triptolide. Angewandte Chemie (International ed. in English) 76 25504624
1996 A 3' --> 5' XPB helicase defect in repair/transcription factor TFIIH of xeroderma pigmentosum group B affects both DNA repair and transcription. The Journal of biological chemistry 75 8663148
2005 TFIIH XPB mutants suggest a unified bacterial-like mechanism for promoter opening but not escape. Nature structural & molecular biology 71 15937491
1997 The XPB subunit of repair/transcription factor TFIIH directly interacts with SUG1, a subunit of the 26S proteasome and putative transcription factor. Nucleic acids research 71 9173976
1994 Characterization of illudin S sensitivity in DNA repair-deficient Chinese hamster cells. Unusually high sensitivity of ERCC2 and ERCC3 DNA helicase-deficient mutants in comparison to other chemotherapeutic agents. Biochemical pharmacology 66 8053936
2004 Phosphorylation of XPB helicase regulates TFIIH nucleotide excision repair activity. The EMBO journal 59 15549133
1994 The DNA-dependent ATPase activity associated with the class II basic transcription factor BTF2/TFIIH. The Journal of biological chemistry 59 7511595
2002 The 14-3-3 proteins Rad24 and Rad25 negatively regulate Byr2 by affecting its localization in Schizosaccharomyces pombe. Molecular and cellular biology 58 12242289
1996 Reconstitution of TFIIH and requirement of its DNA helicase subunits, Rad3 and Rad25, in the incision step of nucleotide excision repair. The Journal of biological chemistry 58 8631896
2014 Laryngeal cancer risk and common single nucleotide polymorphisms in nucleotide excision repair pathway genes ERCC1, ERCC2, ERCC3, ERCC4, ERCC5 and XPA. Gene 57 24582975
2016 Screening of Conditionally Reprogrammed Patient-Derived Carcinoma Cells Identifies ERCC3-MYC Interactions as a Target in Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 56 27384421
2010 The long unwinding road: XPB and XPD helicases in damaged DNA opening. Cell cycle (Georgetown, Tex.) 56 20016270
2006 The DNA repair genes XPB and XPD defend cells from retroviral infection. Proceedings of the National Academy of Sciences of the United States of America 56 16537383
2003 Clear cell tumors have higher mRNA levels of ERCC1 and XPB than other histological types of epithelial ovarian cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 56 14614013
2001 Transcriptional regulation of the TFIIH transcription repair components XPB and XPD by the hepatitis B virus x protein in liver cells and transgenic liver tissue. The Journal of biological chemistry 55 11278765
2002 Hepatitis C virus NS5A protein binds TBP and p53, inhibiting their DNA binding and p53 interactions with TBP and ERCC3. Biochimica et biophysica acta 53 12379483
1995 Efficacy of Acylfulvene Illudin analogues against a metastatic lung carcinoma MV522 xenograft nonresponsive to traditional anticancer agents: retention of activity against various mdr phenotypes and unusual cytotoxicity against ERCC2 and ERCC3 DNA helicase-deficient cells. Cancer research 52 7585533
2008 An Xpb mouse model for combined xeroderma pigmentosum and cockayne syndrome reveals progeroid features upon further attenuation of DNA repair. Molecular and cellular biology 49 19114557
2002 p52 Mediates XPB function within the transcription/repair factor TFIIH. The Journal of biological chemistry 48 12080057
1994 The COOH terminus of suppressor of stem loop (SSL2/RAD25) in yeast is essential for overall genomic excision repair and transcription-coupled repair. The Journal of biological chemistry 47 8294433
2010 UV-induced histone H2AX phosphorylation and DNA damage related proteins accumulate and persist in nucleotide excision repair-deficient XP-B cells. DNA repair 46 20947453
1994 Mutational analysis of ERCC3, which is involved in DNA repair and transcription initiation: identification of domains essential for the DNA repair function. Molecular and cellular biology 46 8196650
1999 The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes. Human molecular genetics 43 10332046
2016 A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer. Cancer discovery 42 27655433
2011 Correlations among ERCC1, XPB, UBE2I, EGF, TAL2 and ILF3 revealed by gene signatures of histological subtypes of patients with epithelial ovarian cancer. Oncology reports 42 21971700
2016 Triptolide Induces Cell Killing in Multidrug-Resistant Tumor Cells via CDK7/RPB1 Rather than XPB or p44. Molecular cancer therapeutics 41 27197304
2006 Polymorphisms in the two helicases ERCC2/XPD and ERCC3/XPB of the transcription factor IIH complex and risk of lung cancer: a case-control analysis in a Chinese population. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 41 16835333
2001 The participation of AtXPB1, the XPB/RAD25 homologue gene from Arabidopsis thaliana, in DNA repair and plant development. The Plant journal : for cell and molecular biology 41 11737776
2000 Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population. Human mutation 39 10862089
1994 Yeast RAD3 protein binds directly to both SSL2 and SSL1 proteins: implications for the structure and function of transcription/repair factor b. Proceedings of the National Academy of Sciences of the United States of America 38 8171014
2022 Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB. Nucleic acids research 37 35947745
2000 Nucleotide excision repair/TFIIH helicases RAD3 and SSL2 inhibit short-sequence recombination and Ty1 retrotransposition by similar mechanisms. Molecular and cellular biology 37 10713167
2013 Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers. Environmental and molecular mutagenesis 34 23797950
2011 MiR-192 inhibits nucleotide excision repair by targeting ERCC3 and ERCC4 in HepG2.2.15 cells. Biochemical and biophysical research communications 33 21672525
1994 The xeroderma pigmentosum group B protein ERCC3 produced in the baculovirus system exhibits DNA helicase activity. Nucleic acids research 33 7937133
2000 Increased mRNA levels of xeroderma pigmentosum complementation group B (XPB) and Cockayne's syndrome complementation group B (CSB) without increased mRNA levels of multidrug-resistance gene (MDR1) or metallothionein-II (MT-II) in platinum-resistant human ovarian cancer tissues. Biochemical pharmacology 32 11077043
1992 Requirement for ERCC-1 and ERCC-3 gene products in DNA excision repair in vitro. Complementation using rodent and human cell extracts. The Journal of biological chemistry 31 1551896
2007 Influence of XPB helicase on recruitment and redistribution of nucleotide excision repair proteins at sites of UV-induced DNA damage. DNA repair 30 17509950
2019 MiR-192-5p reverses cisplatin resistance by targeting ERCC3 and ERCC4 in SGC7901/DDP cells. Journal of Cancer 29 30854110
2005 Transcriptional profiles of unirradiated or UV-irradiated human cells expressing either the cancer-prone XPB/CS allele or the noncancer-prone XPB/TTD allele. Oncogene 29 15608684
2005 Novel interaction of the Hsp90 chaperone machine with Ssl2, an essential DNA helicase in Saccharomyces cerevisiae. Current genetics 29 15871019
1998 Cloning of a cDNA from Arabidopsis thaliana homologous to the human XPB gene. Gene 29 9524267
2024 Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders. Journal of the American Chemical Society 28 38569115
2018 Spironolactone-induced degradation of the TFIIH core complex XPB subunit suppresses NF-κB and AP-1 signalling. Cardiovascular research 28 29036418
2015 XPB: An unconventional SF2 DNA helicase. Progress in biophysics and molecular biology 28 25641424
1992 Cloning and characterization of the Drosophila homolog of the xeroderma pigmentosum complementation-group B correcting gene, ERCC3. Nucleic acids research 28 1454518
1991 Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21. Genomics 27 1916809
2007 The archaeal XPB protein is a ssDNA-dependent ATPase with a novel partner. Journal of molecular biology 26 18177890
2020 Spironolactone and XPB: An Old Drug with a New Molecular Target. Biomolecules 25 32414008
2019 MicroRNA-200c reverses drug resistance of human gastric cancer cells by targeting regulation of the NER-ERCC3/4 pathway. Oncology letters 25 31289483
2012 Tfb6, a previously unidentified subunit of the general transcription factor TFIIH, facilitates dissociation of Ssl2 helicase after transcription initiation. Proceedings of the National Academy of Sciences of the United States of America 25 22411836
2018 Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin. The Journal of investigative dermatology 24 30227140
2009 DNA-dependent ATPase activity of bacterial XPB helicases. Biochemistry 24 19199647
2012 Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB. PloS one 22 22615856
2006 Evaluation of xeroderma pigmentosum XPA, XPC, XPD, XPF, XPB, XPG and DDB2 genes in familial early-onset lung cancer predisposition. International journal of cancer 22 16550608
2004 Functional XPB/RAD25 redundancy in Arabidopsis genome: characterization of AtXPB2 and expression analysis. Gene 22 15656976
2017 Polymorphisms in XRCC1, ERCC2, and ERCC3 DNA repair genes, CYP1A1 xenobiotic metabolism gene, and tobacco are associated with bladder cancer susceptibility in Tunisian population. Environmental science and pollution research international 21 28803404
2013 Structure of the C-terminal half of human XPB helicase and the impact of the disease-causing mutation XP11BE. Acta crystallographica. Section D, Biological crystallography 21 23385459
2000 Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases. Nucleic acids research 21 11071939
2019 Spironolactone-induced XPB degradation depends on CDK7 kinase and SCFFBXL18 E3 ligase. Genes to cells : devoted to molecular & cellular mechanisms 20 30762924
2011 Mechanism of start site selection by RNA polymerase II: interplay between TFIIB and Ssl2/XPB helicase subunit of TFIIH. The Journal of biological chemistry 20 22081613
2002 The regulatory role for the ERCC3 helicase of general transcription factor TFIIH during promoter escape in transcriptional activation. Proceedings of the National Academy of Sciences of the United States of America 20 11818577
2009 Association between genetic variants in VEGF, ERCC3 and occupational benzene haematotoxicity. Occupational and environmental medicine 18 19773279
2003 Alleviation of PC4-mediated transcriptional repression by the ERCC3 helicase activity of general transcription factor TFIIH. The Journal of biological chemistry 18 12590132
1999 Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome. Life sciences 18 10328528
2020 The XPB Subunit of the TFIIH Complex Plays a Critical Role in HIV-1 Transcription and XPB Inhibition by Spironolactone Prevents HIV-1 Reactivation from Latency. Journal of virology 17 33239456
2002 Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells. Cell death and differentiation 17 12232798
1998 Expression of the human XPB/ERCC-3 excision repair gene-homolog in the sponge Geodia cydonium after exposure to ultraviolet radiation. Mutation research 17 9875288
2020 How to limit the speed of a motor: the intricate regulation of the XPB ATPase and translocase in TFIIH. Nucleic acids research 16 33196848
2020 Microtubule associated protein 9 inhibits liver tumorigenesis by suppressing ERCC3. EBioMedicine 15 32151798
2020 ERCC3, a new ovarian cancer susceptibility gene? European journal of cancer (Oxford, England : 1990) 15 33125943
2012 XPB helicase regulates DNA incision by the Thermoplasma acidophilum endonuclease Bax1. DNA repair 14 22237014
2005 Characterization of ERCC3 mutations in the Chinese hamster ovary 27-1, UV24 and MMC-2 cell lines. Mutation research 14 16143348
1996 Comparative analyses of relative ERCC3 and ERCC6 mRNA levels in gliomas and adjacent non-neoplastic brain. Molecular carcinogenesis 14 8876669