Affinage

Showing ERCC3 — XPB is a alias.

ERCC3

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

Length
782 aa
Mass
89.3 kDa
Annotated
2026-06-09
100 papers in source corpus 50 papers cited in narrative 50 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC3/XPB is an essential 3'→5' DNA helicase and DNA-dependent ATPase that operates as a core catalytic subunit of the general transcription factor TFIIH, coupling RNA polymerase II transcription to nucleotide excision repair (NER) (PMID:2167179, PMID:1318786, PMID:7693549, PMID:8663148). It was identified by functional complementation of the NER defect in xeroderma pigmentosum group B and rodent group-3 mutants (PMID:2167179, PMID:2111438, PMID:1551896), and its yeast ortholog SSL2/RAD25 established the gene as essential, with a lethal Walker-A (K392R) ATPase mutation (PMID:1333609) and a conditional allele that simultaneously arrests growth and poly(A)+ RNA synthesis, demonstrating a direct and general role in Pol II transcription (PMID:7693549). Biochemical reconstitution from purified and recombinant subunits showed XPB to be a bona fide DNA helicase (PMID:8202161, PMID:7937133) whose activities are partitioned functionally: the ATPase activity—not helicase translocation per se—drives promoter opening at the transcription start site and damaged-DNA opening during NER, whereas the helicase/translocase activity governs promoter escape, prevents premature arrest of early elongation intermediates, and relieves topological constraints imposed by repressors such as PC4 (PMID:10024882, PMID:10064601, PMID:10428772, PMID:11818577, PMID:12590132, PMID:15937491, PMID:17466626). In yeast, this same ATPase/translocase drives processive transcription start-site scanning, a function absent from human TFIIH (PMID:33453189, PMID:34652274). Within TFIIH, XPB is anchored and its catalytic output regulated by the p52/p8 subcomplex, which stimulates and acts as a dominant speed-limiter of its ATPase, while TFIIE-β co-activates its helicase/ATPase and XPA enhances translocase processivity (PMID:12080057, PMID:15917439, PMID:17466626, PMID:33196848). XPB function in NER requires its C-terminus and coordinates the recruitment and redistribution of downstream NER factors, including ERCC1-XPF for 5' incision (PMID:8294433, PMID:8196650, PMID:17509950, PMID:23385459); phosphorylation of Ser751 selectively blocks NER incision without impairing transcription, separating its two roles post-translationally (PMID:15549133). Structural studies of archaeal and human XPB define tandem RecA-like helicase domains, a DNA damage recognition domain, and the catalytic RED motif, and rationalize disease alleles that reduce XPB solubility and TFIIH levels (PMID:16600867, PMID:23385459). Patient-derived XPB mutations underlie the combined NER/transcription deficiencies of xeroderma pigmentosum group B and XP-B/Cockayne syndrome (PMID:8663148, PMID:10064601, PMID:23385459). XPB Cys342 is the covalent attachment site for triptolide and spironolactone-related compounds that inhibit its ATPase or trigger its degradation, shutting down transcription and NER and providing a chemically validated drug target (PMID:21278739, PMID:25504624, PMID:38569115).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1990 High

    Established the molecular identity of ERCC3 as a candidate DNA helicase and its causal role in a defined repair defect, framing all subsequent mechanistic work.

    Evidence cDNA cloning and transfection complementation of the NER/UDS defect in XP-B and rodent group-3 mutants

    PMID:2111438 PMID:2167179

    Open questions at the time
    • Helicase activity was predicted from sequence motifs, not yet biochemically demonstrated
    • Role in transcription not yet known
  2. 1992 High

    Cross-species genetics (yeast SSL2/RAD25, Drosophila haywire) established ERCC3 as an essential gene whose catalytic ATPase/helicase function is required for viability, not merely repair.

    Evidence Gene deletion, Walker-A K392R lethality, allele analysis, epistasis, and ortholog phenotyping in yeast and flies; in vitro excision-repair complementation in CHO extracts

    PMID:1318786 PMID:1333609 PMID:1458540 PMID:1551896

    Open questions at the time
    • Mechanistic basis of essentiality unresolved
    • Whether essentiality reflects transcription versus repair not yet separated
  3. 1993 High

    Resolved why the gene is essential beyond repair by showing a direct, general requirement in RNA polymerase II transcription.

    Evidence Temperature-sensitive rad25 mutant with collapse of poly(A)+ RNA synthesis at restrictive temperature

    PMID:7693549

    Open questions at the time
    • The specific transcriptional step requiring XPB not yet defined
    • Biochemical activity underlying transcription role unproven
  4. 1994 High

    Demonstrated XPB is itself an ATP-dependent DNA helicase and genetically separated its repair and transcription functions, anchoring its role within TFIIH.

    Evidence Purified/recombinant RAD25 and baculovirus XPB helicase and ssDNA-dependent ATPase assays; repair-defective vs transcription-defective alleles; RAD3-SSL2 in vitro binding; systematic mutagenesis with NER readout

    PMID:7937133 PMID:8171014 PMID:8196650 PMID:8202161 PMID:8294433

    Open questions at the time
    • Whether ATPase or helicase activity drives each substep not yet resolved
    • Regulation of XPB within TFIIH undefined
  5. 1996 High

    Patient-derived TFIIH analysis linked XPB helicase/ATPase loss directly to combined NER and basal transcription defects, and reconstituted yeast TFIIH confirmed XPB is required for incision.

    Evidence Immunopurified XP-B TFIIH with helicase/ATPase, transcription and NER assays; reconstituted yeast TFIIH NER incision with Rad25 ATP-motif mutant

    PMID:8631896 PMID:8663148

    Open questions at the time
    • CTD kinase activity shown dispensable for incision but its broader role unclear
    • Exact catalytic step of XPB in incision not yet pinned
  6. 1999 High

    Defined XPB helicase as absolutely required for promoter opening and for preventing arrest during promoter escape in fully reconstituted transcription systems.

    Evidence TFIIH reconstituted from recombinant subunits with helicase-dead XPB; patient TFIIH promoter-opening assays with artificial-bubble rescue; minimal reconstituted promoter-escape assays

    PMID:10024882 PMID:10064601 PMID:10428772

    Open questions at the time
    • Whether ATP hydrolysis or strand translocation per se opens the promoter not yet distinguished
  7. 2005 High

    Dissected the catalytic logic of XPB: ATPase activity drives promoter opening while helicase translocation drives promoter escape, with TFIIE-β as a co-activator.

    Evidence XPB helicase mutants retaining ATPase activity in in vitro transcription; TFIIE-β mutagenesis and helicase/ATPase stimulation assays

    PMID:15917439 PMID:15937491

    Open questions at the time
    • Structural basis of ATPase-driven opening not yet visualized
    • How TFIIE-β engages XPB structurally undefined
  8. 2007 High

    Extended the ATPase-versus-helicase distinction to NER, showing p52-stimulated XPB ATPase, not helicase, opens damaged DNA, and explained an XP-B patient mutation mechanistically.

    Evidence p52-XPB interaction and ATPase stimulation assays; F99S, T469A, Q638A mutants in reconstituted NER; localization of NER-factor recruitment defects in XPB mutant cells

    PMID:17466626 PMID:17509950

    Open questions at the time
    • Precise sequence of XPF recruitment events not fully ordered
    • How ATPase opening hands off to dual incision unresolved
  9. 2006 High

    Structural studies defined the XPB helicase architecture and damage-modulated substrate specificity, providing a framework for its DNA-opening function.

    Evidence X-ray crystallography of archaeal XPB with RED-motif mutagenesis and helicase assays; later 1.8 Å human XPB C-terminal structure with disease-mutation analysis

    PMID:16600867 PMID:23385459

    Open questions at the time
    • Full-length human XPB structure within intact TFIIH not captured here
    • Structural transitions during catalysis not directly observed
  10. 2004 High

    Identified phosphorylation as a post-translational switch that uncouples XPB's repair and transcription roles.

    Evidence In vivo S751 phosphorylation detection, S751E/S751A mutagenesis, microinjection NER and transcription assays showing selective block of XPF 5' incision

    PMID:15549133

    Open questions at the time
    • Kinase responsible for S751 not identified here
    • Physiological trigger for this switch unknown
  11. 2020 High

    Defined the regulatory hierarchy controlling XPB catalytic speed within TFIIH and the species-specific scanning function.

    Evidence p52/p8 crystal structure with ATPase/translocase assays and XPA stimulation; dsDNA translocase assays comparing yeast and human TFIIH; ssl2 allele TSS mapping

    PMID:33196848 PMID:33453189 PMID:34652274

    Open questions at the time
    • Structural basis of p52/p8 speed-limiting not fully resolved
    • Why human TFIIH lacks processive scanning mechanistically unclear
  12. 2011 High

    Established XPB as a covalently druggable transcription/NER target through triptolide binding and ATPase inhibition.

    Evidence Chemical-biology covalent binding, ATPase and transcription inhibition assays

    PMID:21278739

    Open questions at the time
    • Site of covalent modification not yet mapped at this stage
  13. 2014 High

    Pinpointed Cys342 as the physiologically relevant covalent target and validated XPB as the on-target effector of triptolide.

    Evidence Mass-spec identification of modified Cys342, C342T mutagenesis and CRISPR endogenous replacement conferring resistance

    PMID:25504624

    Open questions at the time
    • Generality of Cys342 targeting by other ligands not yet tested at this stage
  14. 2019 High

    Revealed a regulated degradation route for XPB, defining a phospho-degron and E3 ligase axis exploited by spironolactone.

    Evidence siRNA screening, CDK7-dependent S90 phosphorylation, SCF-FBXL18 ubiquitination assays and proteasome-dependent degradation; chemoproteomic Cys342 modification by spironolactone and ZL-12A

    PMID:29036418 PMID:30762924 PMID:38569115

    Open questions at the time
    • Endogenous physiological signals controlling S90 phosphorylation unknown
    • How distinct Cys342 ligands produce divergent degradation outcomes mechanistically unresolved
  15. 2020 Medium

    Showed XPB is co-opted by viruses for transcription and is targetable pharmacologically to suppress viral gene expression.

    Evidence shRNA knockdown and RNAPII ChIP for HIV-1 transcription/latency; EBV SM-XPB recruitment ChIP with siRNA and spironolactone; retroviral cDNA stability assays in XPB-mutant cells

    PMID:16537383 PMID:32434920 PMID:33239456

    Open questions at the time
    • Direct XPB-viral protein contacts not structurally defined
    • Selectivity of viral promoter recruitment mechanism incompletely mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XPB catalysis is structurally choreographed within intact human TFIIH during the transition from promoter opening to escape, and how its repair-versus-transcription switching is regulated in vivo, remain to be fully defined.
  • No high-resolution structure of catalytic intermediates in human holo-TFIIH captured in this corpus
  • Upstream signaling controlling S751/S90 phosphorylation undefined
  • Mechanistic basis of XPB roles in ATR activation and mRNA export only sketched

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 6 GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 3 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-74160 Gene expression (Transcription) 9 R-HSA-73894 DNA Repair 8
Partners
ERCC1GTF2E2GTF2H4RAD3SUG1TP53XPDXPF
Complex memberships
TFIIH

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 ERCC3 encodes a predicted DNA helicase containing seven consecutive helicase motifs conserved between two superfamilies of DNA and RNA helicases, and specifically corrects the nucleotide excision repair (NER) defect in xeroderma pigmentosum complementation group B (XP-B) rodent mutants. cDNA cloning, transfection complementation assay, sequence analysis Cell High 2167179
1990 ERCC3 cDNA transfection corrects UV sensitivity and unscheduled DNA synthesis (UDS) in complementation group 3 rodent mutants, establishing its role in early steps of the nucleotide excision repair pathway. Transfection/complementation assay, UDS measurement Molecular and cellular biology High 2111438
1992 SSL2 (yeast homolog of ERCC3/XPB) encodes an essential 95 kDa protein with ATP-dependent helicase motifs; an SSL2 allele mimicking the defective ERCC3 gene confers UV hypersensitivity, establishing it as the functional yeast homolog. Gene cloning, mutant allele construction, UV sensitivity assay Cell High 1318786
1992 RAD25 (SSL2) is an essential gene in S. cerevisiae; a mutation in the Walker type A nucleotide-binding motif (K392R) is lethal, indicating an essential role of its ATPase/helicase activity in viability. The gene functions in excision repair (epistasis with excision repair group genes), but not in other repair pathways. Gene deletion, site-directed mutagenesis, epistasis analysis, UV sensitivity assay Proceedings of the National Academy of Sciences of the United States of America High 1333609
1992 The Drosophila haywire gene encodes a protein with 66% identity to ERCC3; haywire mutants are recessive lethal or UV-sensitive, and flies with marginal haywire expression display motor defects and reduced lifespan, establishing the fly ortholog's function in NER and essential cellular processes. Genetic analysis, mutant characterization, UV sensitivity assay Cell High 1458540
1992 Cell-free extracts from CHO ERCC3-deficient (complementation group 3) cells are defective in in vitro DNA excision repair; complementation by mixing with group 1 extracts demonstrates that ERCC3 protein is directly required for enzymatic incision of damaged DNA or preincision reactions. Cell-free excision repair assay, in vitro complementation The Journal of biological chemistry High 1551896
1993 A temperature-sensitive rad25 (SSL2) mutant shows rapid cessation of growth and large decrease in poly(A)+ RNA synthesis at the restrictive temperature, demonstrating a general and direct requirement of RAD25 (XPB ortholog) in RNA polymerase II transcription. Conditional lethal mutant, poly(A)+ RNA measurement, gene-specific Northern blot Genes & development High 7693549
1994 Purified RAD25 (yeast XPB/ERCC3 ortholog) exhibits single-stranded DNA-dependent ATPase and DNA helicase activities. A thermolabile rad25 extract shows transcriptional defect correctable by adding RAD25 protein. The rad25-799am allele (repair-defective) is proficient in RNA Pol II transcription, separating DNA repair from transcription functions. The Arg-392 ATP-binding motif mutant is defective in transcription, implicating helicase activity in promoter opening. Protein purification, in vitro ATPase/helicase assay, in vitro transcription complementation, site-directed mutagenesis Nature High 8202161
1994 The COOH terminus of SSL2/RAD25 is essential for overall genomic NER and transcription-coupled repair; the SSL2-XP allele (resembling the mutated ERCC3 from XP-B/CS-C patients) causes complete deficiency in cyclobutane pyrimidine dimer removal from the overall genome and transcription-coupled repair. Dimer removal assay in expressed genes and genome overall, UV sensitivity The Journal of biological chemistry High 8294433
1994 Mutations in the ATPase motif (helicase domain I), other helicase domains, and the potential helix-turn-helix DNA-binding motif of ERCC3 abolish NER complementation activity; C-terminal deletions implicate a distinct determinant for DNA repair. A functional epitope-tagged ERCC3 accumulates in the nucleus, and deletion of the putative NLS does not impair nuclear localization. Site-directed mutagenesis, deletion mutagenesis, UV complementation assay, immunofluorescence Molecular and cellular biology High 8196650
1994 Recombinant XPB/ERCC3 protein produced in baculovirus system exhibits DNA helicase activity, directly demonstrating that XPB itself is a DNA helicase. Baculovirus expression, protein purification, in vitro helicase assay Nucleic acids research High 7937133
1994 Yeast RAD3 protein directly binds to SSL2 (RAD25/XPB) protein in vitro via an N-terminal, potentially non-catalytic domain of SSL2. A DNA repair-defective allele of SSL2 is not defective in binding to transcription factor b (TFIIH), genetically separating the repair and transcription-binding functions. In vitro immunoprecipitation, yeast two-hybrid, genetic analysis Proceedings of the National Academy of Sciences of the United States of America High 8171014
1994 HBX (hepatitis B virus X protein) complexes with wild-type p53 and inhibits the in vitro association of p53 with ERCC3, as well as p53-mediated transcriptional activation, revealing ERCC3 as a p53-interacting transcription factor. In vitro protein-protein interaction assay, transcription assay Proceedings of the National Academy of Sciences of the United States of America Medium 8134379
1996 TFIIH isolated from XP-B patient cells (XP11BE) carrying a frameshift mutation in XPB shows reduced 3'→5' XPB helicase activity and DNA-dependent ATPase activity, and causes a severe NER defect and decreased basal transcription activity in vitro, establishing that XPB's helicase activity is required for both NER and transcription. Immunopurification of TFIIH, helicase/ATPase assays, in vitro transcription, NER assay The Journal of biological chemistry High 8663148
1996 XPB and XPD are components of the p53-dependent apoptosis pathway: primary fibroblasts from XP-B or XP-D patients (but not XP-A or XP-C) are deficient in p53-mediated apoptosis; this deficiency is rescued by transfer of the wild-type XPB or XPD gene, and the carboxy-terminus of p53 is required for apoptosis. Microinjection of expression vectors, retroviral infection, complementation assay, apoptosis measurement Genes & development High 8675009
1996 Reconstituted yeast TFIIH requires both Rad3 and Rad25 (XPB ortholog) helicase subunits for in vitro NER-mediated incision of UV-damaged DNA; the Rad25 Arg-392 (ATP-binding motif) mutant abolishes NER but not CTD kinase activity, which is dispensable for incision. TFIIH reconstitution, in vitro NER incision assay, mutagenesis The Journal of biological chemistry High 8631896
1997 XPB directly interacts with SUG1 (a subunit of the 26S proteasome), validated by yeast two-hybrid, baculovirus co-expression, co-purification with TFIIH holocomplex, and co-immunoprecipitation; overexpression of SUG1 arrests transcription; a mutant XPB (XP-B patient mutation) shows diminished interaction with SUG1. Yeast two-hybrid, baculovirus co-expression, co-purification, co-immunoprecipitation Nucleic acids research High 9173976
1999 Reconstituted baculovirus-expressed TFIIH with mutated XPB (helicase-dead) is unable to initiate transcription; XPB helicase is absolutely required for promoter opening at the transcription start site, whereas XPD helicase is dispensable but stimulates transcription and anchors CAK to TFIIH. TFIIH reconstitution from recombinant subunits, in vitro transcription, mutagenesis Molecular cell High 10024882
1999 Mutations in XPB found in XP-B/CS patients decrease the transcriptional activity of immunopurified TFIIH by preventing promoter opening; this defect can be circumvented by artificial opening of the promoter, demonstrating that XPB is specifically required for the promoter-opening step in transcription. Immunopurification of patient TFIIH, in vitro transcription, promoter opening assay The EMBO journal High 10064601
1999 XPB helicase activity of TFIIH is primarily responsible for preventing premature arrest of early elongation intermediates during RNA polymerase II promoter escape, demonstrated with TFIIH mutants in a reconstituted minimal transcription system. Reconstituted in vitro transcription system, TFIIH mutant analysis, promoter escape assay The Journal of biological chemistry High 10428772
2002 The p52 subunit of TFIIH physically interacts with XPB and is required to anchor XPB within TFIIH; deletion of the C-terminal region of p52 prevents promoter opening and abolishes NER and transcription activities, demonstrating p52 regulates XPB function through direct interaction. Reconstituted in vitro transcription/NER, deletion mutagenesis, co-immunoprecipitation, domain mapping The Journal of biological chemistry High 12080057
2002 The ERCC3 helicase activity of TFIIH plays a regulatory role in stimulating promoter escape during transcriptional activation; the helicase acts throughout the promoter-escape phase (up to ~10-nt RNA synthesis) to increase the proportion of productive complexes that escape the promoter. Reconstituted in vitro transcription, TFIIH helicase mutants, transcription elongation analysis Proceedings of the National Academy of Sciences of the United States of America High 11818577
2002 HCV NS5A protein inhibits the p53-ERCC3 protein-protein complex formation in vitro, as shown by co-immunoprecipitation and pull-down assays. Co-immunoprecipitation, pull-down assay Biochimica et biophysica acta Low 12379483
2003 The ERCC3 helicase activity of TFIIH alleviates PC4-mediated transcriptional repression via beta-gamma bond hydrolysis of ATP; this requires ERCC3 helicase but not ERCC2 helicase or CDK7 kinase activity, suggesting ERCC3 relieves topological constraints imposed by PC4 at promoters. Reconstituted in vitro transcription, recombinant TFIIH with defined enzymatic mutants The Journal of biological chemistry High 12590132
2004 Serine 751 (S751) of XPB is phosphorylated in vivo; this phosphorylation inhibits NER (a phosphomimicking S751E mutant cannot correct NER defect in XP-B cells) without affecting TFIIH-dependent transcription. S751 phosphorylation does not impair DNA unwinding by TFIIH but prevents 5' incision by ERCC1-XPF endonuclease. In vivo phosphorylation detection, microinjection, NER and transcription assays, mutagenesis (S751E, S751A) The EMBO journal High 15549133
2005 XPB ATPase activity (not helicase activity per se) drives promoter opening for RNA Pol II transcription; XPB helicase mutants that retain ATPase activity are proficient for promoter opening but defective in promoter escape, paralleling sigma54 bacterial transcription. XPB helicase mutant characterization, in vitro transcription assay Nature structural & molecular biology High 15937491
2005 The beta subunit of TFIIE directly stimulates XPB helicase and ATPase activities; TFIIE beta mutants defective for XPB helicase stimulation but competent for PIC assembly are defective in in vitro transcription, establishing TFIIE beta as a co-factor that enhances XPB activity during transcription initiation and promoter escape. In vitro helicase/ATPase assay, mutagenesis of TFIIE beta, reconstituted transcription Nucleic acids research High 15917439
2006 Crystal structures of an archaeal XPB homolog reveal two RecA-like helicase domains, a DNA damage recognition domain (DRD), a unique RED motif, and a flexible thumb motif (ThM). RED motif mutations dramatically reduce helicase activity; the substrate specificity is altered by DNA damage (AfXPB unwinds dsDNA with 3' extensions but not blunt-ended dsDNA unless it contains a lesion). X-ray crystallography, site-directed mutagenesis, in vitro helicase assay Molecular cell High 16600867
2006 XPB DNA repair-deficient cells (XPB/XPD mutants but not XPA mutants) show increased HIV and MLV retroviral transduction efficiency and greater retroviral cDNA stability, establishing a role for TFIIH XPB in degradation of retroviral cDNA as a cellular defense. Retroviral transduction assay, quantitative PCR, XPB mutant cell lines Proceedings of the National Academy of Sciences of the United States of America Medium 16537383
2007 The p52 subunit of TFIIH interacts with XPB and stimulates its ATPase activity; the XP-B patient mutation F99S weakens this interaction and the resulting ATPase stimulation, explaining the damaged DNA opening defect. Mutations in helicase motifs III (T469A) and VI (Q638A) that inhibit XPB helicase activity preserve NER function, demonstrating that XPB ATPase (not helicase) activity drives damaged DNA opening in NER. Protein-protein interaction assay, ATPase assay, mutagenesis, in vitro NER reconstitution Molecular cell High 17466626
2007 Archaeal XPB (from S. solfataricus) is a ssDNA-stimulated ATPase without helicase activity in vitro; XPB physically interacts with a conserved archaeal partner protein Bax1 (encoded by the adjacent gene), establishing a novel XPB-associated endonuclease complex in archaea. ATPase assay, helicase assay, in vitro co-purification/interaction assay Journal of molecular biology Medium 18177890
2007 XPB regulates the recruitment and redistribution of NER proteins at UV damage sites; delayed or absent XPF recruitment is a hallmark of XPB mutations, and redistribution of NER proteins after repair is dependent on functional XPB. Local UV irradiation through micropore filters, fluorescent antibody labeling, live-cell imaging DNA repair Medium 17509950
2010 XPB (p89), but not other TFIIH subunits, re-localizes to centrosomes and adjacent parts of the mitotic spindle during cell division (prophase through telophase); XPB interacts with the centrosomal protein gamma-tubulin; C-terminal truncations of XPB abolish centrosomal association. Immunofluorescence, GFP-fusion live imaging, co-immunoprecipitation, deletion constructs Cellular oncology Medium 20208140
2011 Triptolide covalently binds to human XPB (ERCC3), a subunit of TFIIH, and inhibits its DNA-dependent ATPase activity, leading to inhibition of RNA polymerase II-mediated transcription and NER. Chemical biology binding assay, ATPase inhibition assay, transcription inhibition assay Nature chemical biology High 21278739
2011 XPB functions in ATR kinase activation in non-replicating cells exposed to bulky DNA adducts: genetic and pharmacological inhibition of XPB prevents RPA accumulation on damaged chromatin and abrogates ATR signaling in response to NA-AAF and camptothecin, revealing a role for TFIIH in ATR activation independent of XPA. siRNA knockdown, pharmacological XPB inhibition, immunoblot for ATR substrates, RPA chromatin fractionation The Journal of biological chemistry Medium 28592488
2012 Tfb6, a newly identified TFIIH subunit, forms a heterodimer with Ssl2 (XPB) and facilitates dissociation of Ssl2 from TFIIH after transcription initiation, but does not dissociate Ssl2 from the fully assembled transcription preinitiation complex. TFIIH subunit identification, co-purification, in vitro dissociation assay Proceedings of the National Academy of Sciences of the United States of America Medium 22411836
2013 Crystal structure of the C-terminal half of human XPB (residues 494-782) at 1.8 Å resolution reveals HD2 and a C-terminal extension with structural similarity to RIG-I; this supports a structural model for XPF-XPB-DNA complex for 5' incision. The XP11BE patient mutation reduces XPB solubility and lowers intracellular TFIIH levels, impairing both DNA repair and transcription. X-ray crystallography, Western blot, mutant protein analysis Acta crystallographica. Section D, Biological crystallography High 23385459
2014 Triptolide covalently modifies Cys342 of XPB via its 12,13-epoxide group; mutation of Cys342 to threonine (C342T) confers resistance to triptolide and replacement of endogenous wild-type XPB with C342T in HEK293T cells renders them completely resistant to triptolide, validating XPB as the physiologically relevant target. Mass spectrometry identification of modified residue, site-directed mutagenesis, CRISPR/Cas9 endogenous replacement, cell viability assay Angewandte Chemie (International ed. in English) High 25504624
2014 XPB and XPD bind to G-quadruplex (G4) DNA genome-wide; XPB binds G4 DNA while XPD is a robust G4 helicase; 40% of XPB/XPD ChIP-Seq binding sites overlap with G4 motifs, particularly near transcription start sites of highly transcribed genes. ChIP-Seq in human cells, biochemical G4 binding/helicase assay Nature chemical biology Medium 24609361
2018 Spironolactone (SPL) promotes proteasome-dependent degradation of XPB (but not via mineralocorticoid receptor); proteasome blockade or XPB overexpression prevents SPL-mediated suppression of NF-κB and AP-1 inflammatory signalling; XP patient fibroblasts with N-terminal (but not C-terminal) XPB mutations are insensitive to SPL-mediated XPB degradation. Proteasome inhibitor, siRNA knockdown, XPB overexpression, chromatin immunoprecipitation, patient-derived fibroblasts Cardiovascular research Medium 29036418
2019 Spironolactone-induced XPB degradation requires CDK7 kinase activity and SCFFBXL18 E3 ubiquitin ligase (comprising Skp1, Cul1, FBXL18, and Rbx1); CDK7 phosphorylates XPB at Ser90 to trigger recognition by SCFFBXL18 for polyubiquitination and proteasomal degradation. siRNA library screening, ubiquitination assay, co-immunoprecipitation, site-directed mutagenesis (S90) Genes to cells Medium 30762924
2020 Spironolactone rapidly inhibits HIV-1 transcription by degrading XPB, reducing RNA polymerase II recruitment to the HIV-1 genome; shRNA knockdown of XPB confirmed that XPB degradation is the mechanism of action. SP also inhibits HIV reactivation from latency in resting CD4+ T cells. shRNA knockdown, RNAPII ChIP, HIV transcription assay, latency reactivation assay Journal of virology Medium 33239456
2020 p52/p8 subunits of TFIIH act as master regulators of XPB ATPase activity: XPB ATPase can be activated by DNA or p52/p8, but when both are present p52/p8 dominates and acts as a speed limiter. XPB translocase activity (within core TFIIH) is enhanced by XPA, which increases processivity without altering ATPase rate. ATPase assay, translocase assay, crystal structure of p52/p8, functional mutagenesis, cryo-EM-guided analysis Nucleic acids research High 33196848
2020 EBV SM protein recruits XPB to EBV lytic promoters during lytic replication; depletion of XPB by spironolactone or siRNA inhibits SM-dependent late lytic gene transcription but not other EBV or cellular gene transcription, demonstrating XPB is specifically co-opted for EBV SM-mediated transcriptional activation. ChIP, siRNA knockdown, spironolactone treatment, gene-specific transcription assay Proceedings of the National Academy of Sciences of the United States of America Medium 32434920
2021 The XPB/Ssl2 dsDNA translocase activity drives transcription start-site (TSS) scanning in S. cerevisiae; processive translocation by holo-TFIIH requires the TFIIH kinase module as a processivity factor. Human TFIIH (holo and core) does not exhibit processive translocation, consistent with absence of TSS scanning in humans. dsDNA translocase assay, ATPase assay, holo- vs. core-TFIIH comparison across species Journal of molecular biology High 33453189
2021 Ssl2 (XPB) ATPase activity drives TSS scanning processivity in S. cerevisiae; distinct ssl2 alleles cause upstream or downstream TSS shifts genome-wide; genetic interactions with other initiation factors are consistent with Ssl2 modulating scanning processivity through a conserved residue interaction network. Isolation of novel ssl2 alleles, TSS mapping (PRO-Seq equivalent), genetic interaction analysis eLife High 34652274
2024 A spirocycle acrylamide compound (ZL-12A) covalently reacts with Cys342 of ERCC3 (same residue as triptolide) and promotes ERCC3 degradation as a monofunctional degrader; spironolactone also reacts with ERCC3_C342. ZL-12A and triptolide cross-antagonize each other's protein degradation profiles, demonstrating that covalent ligands targeting the same cysteine can produce distinct functional outcomes. Activity-based protein profiling (ABPP), cysteine-directed chemoproteomics, protein degradation assay, cross-antagonism experiment Journal of the American Chemical Society High 38569115
2007 XPB participates in mRNA export in fission yeast (Ptr8p/XPB); a ptr8-1 temperature-sensitive mutant accumulates poly(A)+ RNA in the nucleus; human XPB rescues both UV sensitivity and mRNA export defects; functional interaction between Ptr8p and Tho2p (TREX complex) was demonstrated. Conditional mutant, poly(A)+ RNA localization, cross-species complementation, co-immunoprecipitation Genes to cells Medium 17212653
2005 Ssl2 (XPB yeast ortholog) interacts with Hsp90 chaperone machinery; multiple SSL2 mutant alleles exhibit pronounced growth defects when co-expressed with mutant Hsp90; Ssl2 protein co-purifies with Hsp90 and Sti1, suggesting Ssl2 function depends on Hsp90. Genetic screen, co-purification, co-immunoprecipitation Current genetics Low 15871019
2011 Ssl2 (XPB) and TFIIB functionally interact in start-site selection and gene looping: an ssl2 suppressor allele (H508R) suppresses the cold-sensitive growth defect and TSS selection defect of the sua7-1 (TFIIB E62K) mutation; Ssl2 associates with both promoter and terminator regions. Genetic suppressor screen, start-site mapping, ChIP The Journal of biological chemistry Medium 22081613

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 417 21278739
1996 The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes & development 303 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 230 17466626
1994 RAD25 is a DNA helicase required for DNA repair and RNA polymerase II transcription. Nature 179 8202161
2014 G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD. Nature chemical biology 167 24609361
1999 Mutations in XPB and XPD helicases found in xeroderma pigmentosum patients impair the transcription function of TFIIH. The EMBO journal 161 10064601
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 142 21571596
1997 A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy. American journal of human genetics 141 9012405
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 127 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 116 1458540
2006 Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome. Human mutation 105 16947863
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) 79 25504624
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
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 60 15549133
2002 The 14-3-3 proteins Rad24 and Rad25 negatively regulate Byr2 by affecting its localization in Schizosaccharomyces pombe. Molecular and cellular biology 59 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
2016 A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer. Cancer discovery 43 27655433
1999 The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes. Human molecular genetics 43 10332046
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
2022 Differential dependencies of human RNA polymerase II promoters on TBP, TAF1, TFIIB and XPB. Nucleic acids research 39 35947745
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
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
2019 MiR-192-5p reverses cisplatin resistance by targeting ERCC3 and ERCC4 in SGC7901/DDP cells. Journal of Cancer 30 30854110
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
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 30 15608684
2018 Spironolactone-induced degradation of the TFIIH core complex XPB subunit suppresses NF-κB and AP-1 signalling. Cardiovascular research 29 29036418
2005 Novel interaction of the Hsp90 chaperone machine with Ssl2, an essential DNA helicase in Saccharomyces cerevisiae. Current genetics 29 15871019
2024 Proteomic Ligandability Maps of Spirocycle Acrylamide Stereoprobes Identify Covalent ERCC3 Degraders. Journal of the American Chemical Society 28 38569115
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
2007 The archaeal XPB protein is a ssDNA-dependent ATPase with a novel partner. Journal of molecular biology 27 18177890
1991 Localization of the xeroderma pigmentosum group B-correcting gene ERCC3 to human chromosome 2q21. Genomics 27 1916809
2020 Spironolactone and XPB: An Old Drug with a New Molecular Target. Biomolecules 26 32414008
2018 Spironolactone Depletes the XPB Protein and Inhibits DNA Damage Responses in UVB-Irradiated Human Skin. The Journal of investigative dermatology 26 30227140
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
2009 DNA-dependent ATPase activity of bacterial XPB helicases. Biochemistry 25 19199647
2012 Enzymatic activities and DNA substrate specificity of Mycobacterium tuberculosis DNA helicase XPB. PloS one 23 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
2019 Spironolactone-induced XPB degradation depends on CDK7 kinase and SCFFBXL18 E3 ligase. Genes to cells : devoted to molecular & cellular mechanisms 21 30762924
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
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
2020 How to limit the speed of a motor: the intricate regulation of the XPB ATPase and translocase in TFIIH. Nucleic acids research 18 33196848
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 18 33239456
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
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 ERCC3, a new ovarian cancer susceptibility gene? European journal of cancer (Oxford, England : 1990) 16 33125943
2020 Microtubule associated protein 9 inhibits liver tumorigenesis by suppressing ERCC3. EBioMedicine 15 32151798
2021 The Role of XPB/Ssl2 dsDNA Translocase Processivity in Transcription Start-site Scanning. Journal of molecular biology 14 33453189
2017 DNA damage-induced ATM- and Rad-3-related (ATR) kinase activation in non-replicating cells is regulated by the XPB subunit of transcription factor IIH (TFIIH). The Journal of biological chemistry 14 28592488
2012 XPB helicase regulates DNA incision by the Thermoplasma acidophilum endonuclease Bax1. DNA repair 14 22237014
2005 Stimulation of the XPB ATP-dependent helicase by the beta subunit of TFIIE. Nucleic acids research 14 15917439
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
2021 Ssl2/TFIIH function in transcription start site scanning by RNA polymerase II in Saccharomyces cerevisiae. eLife 13 34652274
2020 Epstein-Barr virus co-opts TFIIH component XPB to specifically activate essential viral lytic promoters. Proceedings of the National Academy of Sciences of the United States of America 13 32434920
2013 Trypanosoma brucei harbours a divergent XPB helicase paralogue that is specialized in nucleotide excision repair and conserved among kinetoplastid organisms. Molecular microbiology 13 24134817
1999 Molecular characterization of mutant alleles of the DNA repair/basal transcription factor haywire/ERCC3 in Drosophila. Genetics 13 10224261
2017 Association between Promoter Methylation of Gene ERCC3 and Benzene Hematotoxicity. International journal of environmental research and public health 12 28813025
2010 The TFIIH subunit p89 (XPB) localizes to the centrosome during mitosis. Cellular oncology : the official journal of the International Society for Cellular Oncology 12 20208140
2007 Participation of XPB/Ptr8p, a component of TFIIH, in nucleocytoplasmic transport of mRNA in fission yeast. Genes to cells : devoted to molecular & cellular mechanisms 12 17212653

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