Affinage

ERCC2

General transcription and DNA repair factor IIH helicase subunit XPD · UniProt P18074

Length
760 aa
Mass
86.9 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ERCC2/XPD is an ATP-dependent 5'-to-3' DNA helicase that functions as a core subunit of the RNA polymerase II transcription factor TFIIH, coordinating nucleotide excision repair (NER) with transcription (PMID:8194528, PMID:25268380). Its catalytic core comprises two RecA-like helicase domains (HD1, HD2), an Arch domain, and an N-terminal [4Fe-4S] cluster domain coordinated by conserved cysteines that is strictly required for helicase activity (PMID:16973432, PMID:18510924, PMID:18510925). Within TFIIH, XPD's helicase activity—dependent on DNA binding, ATPase function, and 4Fe-4S domain integrity, and stimulated by the p44 subunit—is devoted exclusively to NER and is dispensable for transcription initiation, where XPD instead acts as a structural scaffold (PMID:25268380). During lesion processing XPD verifies damage identity while loading DNA through a pore via a tightly held Arch–4FeS interface and a transient opening that exposes a second DNA-binding site (PMID:26896802), and damage discrimination involves coordinated Arch, FeS, and ATPase-domain movements that stall XPD at lesions (PMID:35713557). Through its Arch domain XPD anchors the CDK-activating kinase (CAK; CDK7–cyclin H–MAT1) to TFIIH, contacting MAT1 to link NER and transcription with cell-cycle and nuclear-receptor-mediated transactivation (PMID:32245994, PMID:23232694), and regulation of CAK localization and activity by XPD controls mitotic progression (PMID:12853965, PMID:20300654). Independently of TFIIH, XPD assembles into the MMXD complex (MMS19, MIP18/FAM96B, Ciao1, ANT2) at the mitotic spindle to ensure proper chromosome segregation (PMID:20797633), localizes to mitochondria where it interacts with TUFM to protect mtDNA from oxidative damage (PMID:25969448), and acts in the p53-dependent apoptotic response to DNA damage (PMID:8675009). Distinct XPD mutations produce the clinically distinct phenotypes xeroderma pigmentosum and trichothiodystrophy depending on the affected domain and the second allele (PMID:9238033), and loss-of-function somatic ERCC2 mutations in urothelial carcinoma impair NER and confer cisplatin sensitivity (PMID:25096233).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1994 High

    Established that ERCC2/XPD is a functional subunit of TFIIH, physically linking it to both NER and RNA polymerase II transcription and explaining why a repair gene also affects transcription.

    Evidence Co-purification, reciprocal immunoprecipitation, and transcription reconstitution of ERCC2 with BTF2/TFIIH

    PMID:8194528

    Open questions at the time
    • Did not resolve the catalytic mechanism within TFIIH
    • Did not separate transcription vs. repair contributions
  2. 1996 High

    Placed XPD specifically in the p53-dependent apoptotic pathway downstream of p53 and upstream of caspases, distinguishing it from other XP factors.

    Evidence p53 microinjection and genetic complementation with wild-type XPD in patient fibroblasts, with epistasis across XP complementation groups

    PMID:8675009

    Open questions at the time
    • Molecular mechanism linking XPD to p53 apoptosis not defined
    • Whether this depends on helicase or TFIIH function unknown
  3. 1997 High

    Showed that distinct XPD mutations cause distinct clinical syndromes (XP vs. TTD) and that phenotype is allele-dependent, framing XPD as a gene where mutation position dictates which TFIIH function is compromised.

    Evidence Patient cDNA sequencing and allele-specific yeast complementation

    PMID:9238033

    Open questions at the time
    • Structural basis of XP vs. TTD mutation effects not yet known
    • Mechanism of allele interaction unexplained
  4. 2003 High

    Revealed that XPD negatively regulates CAK activity and is downregulated at mitotic onset, connecting XPD dosage to cell-cycle progression beyond its repair role.

    Evidence Drosophila gain- and loss-of-function genetics with Cdk T-loop phosphorylation readouts; insulin/RAS-pathway regulation of XPD levels shown separately in CHO cells

    PMID:12706296 PMID:12853965

    Open questions at the time
    • Direct biochemical mechanism of CAK inhibition by XPD not resolved
    • Mammalian relevance of mitotic downregulation untested
  5. 2006 Medium

    Defined the [4Fe-4S] cluster domain as essential for helicase activity and NER, and revealed an unexpected TFIIH-linked role in degrading retroviral cDNA distinct from canonical NER.

    Evidence Fe-S cluster characterization, cysteine mutagenesis and helicase assays with yeast UV-repair complementation; retroviral transduction assays in XPB/XPD/XPA mutant cells

    PMID:16537383 PMID:16973432

    Open questions at the time
    • How the Fe-S cluster contributes mechanically to unwinding not fully defined
    • Mechanism of retroviral cDNA degradation by XPB/XPD unknown
  6. 2008 High

    Provided the structural framework: a four-domain catalytic core (HD1, HD2, 4FeS, Arch) with 5'-to-3' polarity, mapping disease mutations to functional regions and explaining XP, XP/CS, and TTD phenotypes.

    Evidence Two independent X-ray crystal structures of archaeal XPD with biochemical helicase assays and disease-mutation mapping

    PMID:18510924 PMID:18510925

    Open questions at the time
    • Structures are archaeal, not human TFIIH-bound
    • Dynamic conformational changes during catalysis not captured
  7. 2010 High

    Identified a TFIIH-independent function for XPD in chromosome segregation through the MMXD complex at the mitotic spindle, broadening XPD's role beyond repair and transcription.

    Evidence MMXD complex purification/MS, reciprocal Co-IP, siRNA segregation phenotypes, and patient-cell analysis; Drosophila imaging of Cdk7/CAK mislocalization upon Xpd loss

    PMID:20300654 PMID:20797633

    Open questions at the time
    • Direct molecular role of XPD within MMXD at the spindle unclear
    • How XPD partitions between TFIIH and MMXD not defined
  8. 2011 Medium

    Linked the 4Fe-4S cluster to ATP-stimulated DNA-mediated redox signaling and synthesized a mechanistic model of asymmetric DNA unwinding with XPD as the damage-verification helicase anchoring CAK.

    Evidence DNA-modified electrochemistry of XPD redox potential; structural-biochemical review synthesizing the XPB/XPD unwinding model

    PMID:21571596 PMID:21939244

    Open questions at the time
    • Redox signaling shown in vitro only, no independent replication
    • Physiological role of redox signaling untested in cells
  9. 2014 High

    Cleanly separated XPD's helicase function (exclusively for NER, p44-stimulated) from its scaffolding role in transcription, and demonstrated that loss-of-function ERCC2 mutations in urothelial cancer drive cisplatin sensitivity.

    Evidence Comparative biochemistry/mutagenesis of human and C. thermophilum XPD; functional complementation of tumor-derived ERCC2 mutants in ERCC2-deficient cells; arsenic-induced ERCC2 dysregulation via Cdk7 association

    PMID:24473091 PMID:25096233 PMID:25268380

    Open questions at the time
    • How transcription proceeds without XPD catalytic activity not fully detailed
    • In vivo predictive value of cancer mutations for therapy response not established here
  10. 2015 Medium

    Demonstrated a mitochondrial role: XPD localizes to the inner mitochondrial membrane, interacts with TUFM, and protects mtDNA from oxidative damage, extending XPD function beyond the nucleus.

    Evidence Subcellular fractionation, immunofluorescence, siRNA, mtDNA deletion and oxidative-repair assays, and IP-MS identifying TUFM

    PMID:25969448

    Open questions at the time
    • Catalytic mechanism of XPD in mtDNA protection unknown
    • Functional significance of TUFM interaction not mechanistically resolved
  11. 2016 High

    Resolved the DNA loading mechanism, showing sequential engagement of HD2 then transient Arch–4FeS opening to thread DNA through the pore onto HD1.

    Evidence Crystal structure of HD2-deleted archaeal XPD with cross-linking and biochemical DNA-binding assays

    PMID:26896802

    Open questions at the time
    • Loading kinetics in the context of full TFIIH not addressed
    • Coupling to XPB translocation not resolved
  12. 2020 High

    Established the Arch domain–MAT1 interaction as mechanistically essential for both NER and transcription, unifying XPD's dual roles through a single structural interface.

    Evidence Crystal structure of the XPD Arch–MAT1 complex with interface mutagenesis and NER, helicase, XPD–XPG interaction, and RNAP II phosphorylation assays

    PMID:32245994

    Open questions at the time
    • How CAK release/retention is dynamically regulated during repair not defined
    • Link to nuclear-receptor transactivation only indirectly addressed
  13. 2022 Low

    Proposed atomic-level residues and domain motions underlying damage verification and lesion-induced stalling of human XPD.

    Evidence All-atom molecular dynamics simulations of human XPD with undamaged and 6-4PP-containing ssDNA

    PMID:35713557

    Open questions at the time
    • Computational only — identified residues not experimentally validated in this study
    • Predicted dynamics not confirmed structurally or biochemically

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how XPD dynamically partitions among its TFIIH, MMXD, mitochondrial, and apoptotic functions, and how upstream signals regulate XPD abundance and localization to coordinate these roles.
  • Mechanism partitioning XPD between TFIIH and MMXD unknown
  • Regulation of mitochondrial recruitment incompletely defined
  • Cancer-relevant signaling control of XPD levels not mechanistically unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 4 GO:0140657 ATP-dependent activity 4 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2 GO:0016787 hydrolase activity 1
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CDK7CIAO1ERCC3FAM96BGTF2H1MAT1MMS19TUFM
Complex memberships
CAK (CDK7-cyclin H-MAT1)MMXD complexTFIIH

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 ERCC2/XPD protein co-purifies with the RNA polymerase II transcription factor BTF2/TFIIH; antibodies against ERCC3 (p89) or p62 subunit of BTF2 can immunoprecipitate ERCC2, and conversely an anti-ERCC2 antibody retains BTF2. ERCC2 can be salt-resolved from other BTF2 components, and its re-addition enhances BTF2 transcription activity, indicating ERCC2 is a functional subunit of TFIIH involved in both NER and transcription. Co-purification, immunoprecipitation, glycerol gradient sedimentation, transcription activity reconstitution The EMBO journal High 8194528
1996 XPD (ERCC2) and XPB are components of the p53-mediated apoptosis pathway. Primary fibroblasts from XP-D patients (deficient in XPD) have a deficiency in p53-induced apoptosis that can be rescued by transferring wild-type XPD gene into the mutant cells. XP-D lymphocytes also show decreased apoptotic response to DNA damage by adriamycin. XP-A and XP-C mutant cells do not show this apoptotic deficiency, placing XPD specifically in the p53 apoptotic pathway downstream of p53 but upstream of ICE-family caspases. Microinjection of p53 expression vector into primary fibroblasts, retroviral infection, genetic complementation with wild-type XPD gene, comparison across XP complementation groups Genes & development High 8675009
2003 Drosophila Xpd negatively regulates CAK (Cdk7-cyclin H-MAT1) activity within TFIIH. Excess Xpd titrates CAK activity, resulting in decreased Cdk T-loop phosphorylation, mitotic defects, and lethality; conversely, reduced Xpd increases CAK activity and cell proliferation. Xpd is downregulated at the onset of mitosis, which appears to upregulate mitotic CAK activity and promotes mitotic progression. Drosophila genetics (overexpression and loss-of-function), Cdk T-loop phosphorylation assays, mitosis/lethality phenotype analysis Nature High 12853965
2006 XPD (and FancJ) contain a conserved iron-sulfur (Fe-S) cluster domain near the N-terminus coordinated by three absolutely conserved cysteine residues; this Fe-S cluster is essential for XPD helicase activity. Yeast strains with mutations in the Fe-S domain of Rad3 (yeast XPD ortholog) are defective in UV photoproduct excision repair. Clinically relevant TTD mutations disrupt the Fe-S cluster and abolish helicase activity. Biochemical Fe-S cluster characterization, site-directed mutagenesis of cysteine ligands, in vitro helicase assays, yeast genetic complementation/UV repair assay Molecular cell High 16973432
2008 Crystal structure of XPD catalytic core (from Sulfolobus acidocaldarius) reveals four domains: two Rad51/RecA-like helicase domains (HD1, HD2), a 4FeS domain, and an Arch domain forming a substrate-binding groove. XP mutations along HD1 ATP-binding edge and HD2 DNA-binding channel impair helicase activity essential for NER. XP/CS mutations both impair helicase activity and likely affect HD2 functional movement. TTD mutants map to sites in all four domains causing framework defects that impair TFIIH integrity. X-ray crystallography, in vitro helicase activity assays, mutation analysis Cell High 18510924
2008 2.25 Å crystal structure of XPD from Sulfolobus tokodaii confirms four-domain organization and reveals that XPD has 5'-to-3' polarity; helicase activity is dependent on the iron-sulfur cluster binding domain. Detailed biochemical analyses provide molecular basis for helicase mechanism and explain phenotypes of XPD mutations in humans. X-ray crystallography (2.25 Å), biochemical helicase assays Cell High 18510925
2010 XPD forms a TFIIH-independent protein complex called MMXD containing MMS19, MIP18 (FAM96B), Ciao1, and ANT2. MMS19, MIP18, and XPD localize to the mitotic spindle during mitosis. siRNA knockdown of MMS19, MIP18, or XPD causes improper chromosome segregation and accumulation of nuclei with abnormal shapes. XP-D and XP-D/CS patient cells also show increased frequency of abnormal mitosis. Protein complex purification/mass spectrometry, co-immunoprecipitation, siRNA knockdown, immunofluorescence localization during mitosis, analysis of patient cells Molecular cell High 20797633
2010 Drosophila Xpd regulates Cdk7 (CAK) subcellular localization during mitosis: loss of Xpd causes mislocalization of Cdk7/CAK and altered local mitotic kinase activity, leading to defects in spindle dynamics, improper chromosome segregation, multipolar spindles, and aneuploidy. This function is independent of NER and transcription. Drosophila genetics (xpd loss-of-function in early embryos), live imaging, immunofluorescence of Cdk7 localization, kinase activity assays, chromosome segregation analysis PLoS genetics High 20300654
2011 XPD generates ATP-stimulated, DNA-mediated redox signaling via its [4Fe-4S] cluster. Using DNA-modified electrodes, XPD shows a DNA-bound redox potential of ~80 mV vs. NHE, similar to base excision repair proteins. The redox signal increases with ATP hydrolysis and is substrate-dependent, reporting on DNA conformational changes associated with enzymatic function. DNA-modified electrochemical electrodes, redox signal measurement, ATP hydrolysis assay Journal of the American Chemical Society Medium 21939244
2011 XPB and XPD helicases within TFIIH asymmetrically unwind dsDNA flanking DNA damage; XPD anchors the CAK kinase complex (cyclinH, MAT1, CDK7) to TFIIH, coordinating NER with transcription and cell cycle through CAK signaling. XPB acts as an ATPase/translocase to open DNA at the damage site, while XPD verifies damage identity. Structural biology review integrating crystal structures, NMR, and EM data with biochemical and cellular information; functional model synthesis DNA repair Medium 21571596
2014 In TFIIH, XPD helicase activity (requiring DNA binding, ATPase, and 4Fe4S domain integrity) is exclusively devoted to NER and is dispensable for transcription initiation. The p44 subunit activates XPD by stimulating its ATPase activity. Mutations in the 4Fe4S cluster domain abolish NER without affecting transcriptional activity of TFIIH. Comparative biochemical analysis (in vitro and in vivo) of human and Chaetomium thermophilum XPD; ATPase assays, NER complementation assays, transcription assays, mutagenesis of 4Fe4S domain PLoS biology High 25268380
2014 Somatic ERCC2 mutations in muscle-invasive urothelial carcinoma impair NER function: expression of representative ERCC2 tumor-derived mutants in an ERCC2-deficient cell line failed to rescue cisplatin sensitivity and UV sensitivity compared with wild-type ERCC2, demonstrating loss of normal ERCC2 function contributes to cisplatin sensitivity. Whole-exome sequencing of patient tumors, functional complementation of ERCC2-deficient cells with mutant vs. wild-type ERCC2, cisplatin and UV cytotoxicity assays Cancer discovery High 25096233
2015 XPD localizes to the inner membrane of mitochondria; oxidative stress enhances XPD recruitment into the mitochondrial compartment. Knockdown of XPD in U2OS cells or XPD-deficient fibroblasts increases mitochondrial ROS, elevates mtDNA common deletion levels, and reduces oxidative damage repair capacity in mtDNA. Immunoprecipitation-mass spectrometry identified TUFM (mitochondrial Tu translation elongation factor) as a physical interaction partner of XPD in mitochondria; TUFM knockdown phenocopies XPD deficiency for mtDNA damage. Subcellular fractionation/Western blot, immunofluorescence localization, siRNA knockdown, mtDNA common deletion assay, oxidative damage repair assay, immunoprecipitation-mass spectrometry Nucleic acids research Medium 25969448
2016 DNA loading by XPD proceeds via initial tight ssDNA binding to helicase domain 2, followed by transient opening of the Arch–4FeS domain interface allowing access to a second binding site on helicase domain 1 that directs DNA through the pore. Crystal structure of Sulfolobus acidocaldiarius XPD lacking helicase domain 2 shows otherwise unperturbed architecture, emphasizing the stability of the Arch–4FeS interface. X-ray crystallography, chemical cross-linking, modified DNA substrates, biochemical binding assays Nucleic acids research High 26896802
2020 The Arch domain of XPD interacts with MAT1 (a component of the CDK-activating kinase complex); mutagenesis of the Arch–MAT1 interface impairs both NER (by reducing helicase activity or disrupting XPD–XPG interaction) and RNA polymerase II phosphorylation/RNA synthesis, demonstrating the Arch domain is mechanistically essential for both NER and transcription within TFIIH. Crystal structure of XPD Arch domain with MAT1, mutagenesis of interface residues, NER complementation assay, XPD helicase assay, XPD–XPG interaction assay, RNA synthesis/RNAP II phosphorylation assays Nature communications High 32245994
2014 Arsenic exposure leads to promoter hypomethylation of ERCC2 and ~2-fold overexpression of ERCC2 protein, but this overexpression causes increased association of Cdk7 with ERCC2 (demonstrated by immunoprecipitation/Western blot), resulting in decreased CAK activity (reduced Ser392-p53 phosphorylation) and impaired DNA repair despite higher ERCC2 levels. Bisulfite-methylation-specific PCR, immunoprecipitation/Western blot, in vitro CAK activity assay (p53 Ser392 phosphorylation), micronuclei assay Metallomics Medium 24473091
1997 Different mutations in the XPD/ERCC2 gene produce distinct clinical phenotypes (XP vs. TTD). Allele-specific yeast complementation assays showed that the same nucleotide change at certain positions can cause either XP or TTD depending on the second allele; null mutations at shared positions indicate that the phenotype is determined by the other (non-null) allele. Most TTD mutations cluster in a region (amino acids 713–730 and helicase motif areas) distinct from typical XP mutations. ERCC2 cDNA sequencing from patient cell lines, yeast complementation assay of individual alleles Proceedings of the National Academy of Sciences High 9238033
2006 XPB (ERCC3) and XPD (ERCC2) play a principal role in the degradation of retroviral cDNA in the nucleus. XPB and XPD mutant cells exhibit increased transduction efficiency by HIV- and MLV-based retroviral vectors, increased total cDNA, integrated provirus, and 2-LTR circles. XPA mutant cells do not show this effect, placing the function specifically in XPB/XPD but not the broader NER pathway. Retroviral transduction assays in XPB/XPD/XPA mutant cell lines, quantitative PCR for cDNA/integration/2-LTR circles, reverse transcription inhibitor experiments Proceedings of the National Academy of Sciences Medium 16537383
2022 MD simulations of human XPD bound to ssDNA containing a (6-4)PP UV photoproduct identify key residues involved in damage verification: FeS domain residues R112, R196, H135, K128; Arch domain residues E377 and R380; and ATPase lobe 1 residues 215–221. Arch and ATPase lobe 1 domain movements relative to the FeS domain modulate DNA–residue interactions to discriminate damaged from undamaged nucleotides, leading to XPD stalling at the lesion. All-atom molecular dynamics simulations of human XPD with undamaged and 6-4PP-damaged ssDNA Nucleic acids research Low 35713557
2003 Insulin regulates XPD expression via the RAS-signaling and p70 S6 kinase pathways in CHO cells transfected with the human insulin receptor. The intracellular XPD protein level is under exclusive control of the RAS-dependent cascade in response to insulin. Short-term high glucose potentiates insulin-dependent XPD regulation and protects against glucose-induced DNA damage, while chronic high glucose impairs insulin's ability to regulate XPD, leading to accumulation of DNA damage. Signaling pathway inhibitor experiments (RAS, p70 S6 kinase), Western blot, qRT-PCR, comet assay in CHO cells with human insulin receptor Molecular and cellular endocrinology Medium 12706296
2012 XPD mutations are associated with abnormal TFIIH-dependent transactivation of nuclear receptor for vitamin D (VDR). Cells from TTD, XP, and XP/TTD patients with specific XPD mutation pairs showed reduced (5 patients) or elevated (1 patient) vitamin D stimulation ratios of CYP24 and osteopontin, demonstrating that XPD serves as a structural bridge between TFIIH core and the CAK complex to regulate nuclear receptor-mediated transcription. Nuclear receptor transactivation reporter assays (CYP24, osteopontin expression after vitamin D stimulation) in primary patient fibroblasts from XPD compound heterozygotes European journal of human genetics Medium 23232694
2019 XPD suppresses HCC cell proliferation and migration via regulation of miR-29a-3p expression. miR-29a-3p directly targets Mdm2 and PDGF-B (confirmed by dual-luciferase reporter assay), and XPD suppresses proliferation and migration of HCC cells through this XPD→miR-29a-3p→Mdm2/PDGF-B axis. Western blot, qRT-PCR, MTT proliferation assay, transwell migration assay, dual-luciferase reporter assay for miR-29a-3p targets Cell & bioscience Low 30627419
2019 XPD-mutated cell lines (XP, XP-D/CS, TTD) are sensitive to oxidative stress (photoactivated methylene blue and KBrO3). XP-D/CS and TTD cells have severely impaired repair capacity for oxidized lesions in plasmid DNA (host cell reactivation assay) and accumulate more DNA strand breaks after oxidative treatment than wild-type, with persistent γ-H2AX and S/G2 arrest, demonstrating XPD participates in repair of oxidatively-induced DNA lesions. Host cell reactivation assay, alkaline comet assay, γ-H2AX immunofluorescence, cell cycle analysis, survival assays in patient-derived XPD-mutated cell lines Mutagenesis Medium 31348825
2023 NOP2-mediated m5C methylation of XPD mRNA elevates XPD mRNA stability and expression. NOP2 overexpression in HCC cells enhances XPD expression by increasing m5C methylation of XPD mRNA, which inhibits proliferation, migration, and invasion of HCC cells in vitro. In vitro cell overexpression, m5C methylation assay, Western blot, proliferation/migration/invasion assays Neoplasma Low 37498063

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma. Cancer discovery 514 25096233
2001 XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 404 11532866
2000 XPD polymorphisms: effects on DNA repair proficiency. Carcinogenesis 373 10753184
1994 The ERCC2/DNA repair protein is associated with the class II BTF2/TFIIH transcription factor. The EMBO journal 342 8194528
2008 XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. Cell 311 18510924
1996 The XPB and XPD DNA helicases are components of the p53-mediated apoptosis pathway. Genes & development 303 8675009
1992 ERCC1 and ERCC2 expression in malignant tissues from ovarian cancer patients. Journal of the National Cancer Institute 289 1433335
2006 The DNA repair helicases XPD and FancJ have essential iron-sulfur domains. Molecular cell 277 16973432
1997 Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene. Proceedings of the National Academy of Sciences of the United States of America 233 9238033
2008 Structure of the DNA repair helicase XPD. Cell 220 18510925
2002 ERCC2/XPD gene polymorphisms and cancer risk. Mutagenesis 189 12435843
2000 XPD/ERCC2 polymorphisms and risk of head and neck cancer: a case-control analysis. Carcinogenesis 174 11133811
2006 XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. American journal of epidemiology 166 16707649
2003 Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 160 12692111
2005 ERCC2 /XPD gene polymorphisms and lung cancer: a HuGE review. American journal of epidemiology 147 15615908
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
2001 Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma. Carcinogenesis 118 11238179
2004 DNA repair gene XRCC1 and XPD polymorphisms and risk of prostate cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 112 14744728
2003 Xpd/Ercc2 regulates CAK activity and mitotic progression. Nature 106 12853965
2010 MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation. Molecular cell 104 20797633
1996 Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy. American journal of human genetics 96 8571952
2002 DNA repair gene ERCC1 and ERCC2/XPD polymorphisms and risk of squamous cell carcinoma of the head and neck. Archives of otolaryngology--head & neck surgery 94 12220217
2005 Polymorphisms in the human XPD (ERCC2) gene, DNA repair capacity and cancer susceptibility: an appraisal. DNA repair 92 16054878
2014 In TFIIH, XPD helicase is exclusively devoted to DNA repair. PLoS biology 76 25268380
2001 XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis 76 11470747
2004 DNA repair gene XPD polymorphism and lung cancer risk: a meta-analysis. Lung cancer (Amsterdam, Netherlands) 71 15364127
2005 Genetic variation in XPD, sun exposure, and risk of skin cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 68 15941969
2005 Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells. Mutagenesis 65 16195314
2005 ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro-oncology 63 16212814
1992 The XPD complementation group. Insights into xeroderma pigmentosum, Cockayne's syndrome and trichothiodystrophy. Mutation research 63 1372108
1983 The relationship between sister-chromatid exchange and perturbations in DNA replication in mutant EM9 and normal CHO cells. Mutation research 62 6843572
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
2005 Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer 56 15834925
2018 DNA translocation mechanism of an XPD family helicase. eLife 55 30520735
2008 DNA repair gene XPD and XRCC1 polymorphisms and the risk of childhood acute lymphoblastic leukemia. Leukemia research 53 19101034
2004 XPD gene polymorphism and host characteristics in the association with cutaneous malignant melanoma risk. British journal of cancer 53 14735199
2015 XPD localizes in mitochondria and protects the mitochondrial genome from oxidative DNA damage. Nucleic acids research 52 25969448
1994 Altered DNA ligase III activity in the CHO EM9 mutant. Mutation research 51 7510367
1984 DNA-ligase activities appear normal in the CHO mutant EM9. Mutation research 51 6738565
2016 Role of XPD in cellular functions: To TFIIH and beyond. DNA repair 50 27262611
2007 XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis 50 17264068
2006 Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 50 16492913
2011 ATP-stimulated, DNA-mediated redox signaling by XPD, a DNA repair and transcription helicase. Journal of the American Chemical Society 49 21939244
2004 Polymorphisms in XPD and TP53 and mutation in human lung cancer. Carcinogenesis 48 15564288
1998 The CHO XRCC1 mutant, EM9, deficient in DNA ligase III activity, exhibits hypersensitivity to camptothecin independent of DNA replication. Mutation research 47 9739812
2010 ERCC2/XPD Lys751Gln and Asp312Asn gene polymorphism and lung cancer risk: a meta-analysis involving 22 case-control studies. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 46 20651612
1994 Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene. Human molecular genetics 42 7849702
2014 Arsenic-induced promoter hypomethylation and over-expression of ERCC2 reduces DNA repair capacity in humans by non-disjunction of the ERCC2-Cdk7 complex. Metallomics : integrated biometal science 41 24473091
2004 Effect of XPD/ERCC2 polymorphisms on chromosome aberration frequencies in smokers and on sensitivity to the mutagenic tobacco-specific nitrosamine NNK. Environmental and molecular mutagenesis 41 15199548
1992 Construction of human XRCC1 minigenes that fully correct the CHO DNA repair mutant EM9. Nucleic acids research 41 1408759
2010 Meta-analysis of two ERCC2 (XPD) polymorphisms, Asp312Asn and Lys751Gln, in breast cancer. Breast cancer research and treatment 40 20379847
2010 Genotoxic and apoptotic activities of the food flavourings myristicin and eugenol in AA8 and XRCC1 deficient EM9 cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 40 21087650
2006 XPD common variants and their association with melanoma and breast cancer risk. Breast cancer research and treatment 40 16685590
2016 Mechanism of DNA loading by the DNA repair helicase XPD. Nucleic acids research 39 26896802
2009 Polymorphisms of DNA repair genes: ADPRT, XRCC1, and XPD and cancer risk in genetic epidemiology. Methods in molecular biology (Clifton, N.J.) 39 19109787
2007 Polymorphisms of DNA repair genes XPD and XRCC1 and risk of cataract development. Experimental eye research 39 17637462
2004 Polymorphisms in the DNA repair gene XPD and susceptibility to esophageal squamous cell carcinoma. Cancer genetics and cytogenetics 39 15381366
2020 In TFIIH the Arch domain of XPD is mechanistically essential for transcription and DNA repair. Nature communications 38 32245994
1987 Induction and repair of DNA single-strand breaks in EM9 mutant CHO cells treated with hydrogen peroxide. Chemico-biological interactions 38 3115605
2013 ERCC1 and ERCC2 variants predict survival in gastric cancer patients. PloS one 35 24023723
2010 Drosophila Xpd regulates Cdk7 localization, mitotic kinase activity, spindle dynamics, and chromosome segregation. PLoS genetics 35 20300654
2008 ERCC1 and ERCC2 polymorphisms and risk of idiopathic azoospermia in a Chinese population. Reproductive biomedicine online 33 18616887
2004 The DNA repair gene ERCC2/XPD polymorphism Arg 156Arg (A22541C) and risk of lung cancer in a Chinese population. Cancer letters 33 15896456
1995 Characteristics of UV-induced mutation spectra in human XP-D/ERCC2 gene-mutated xeroderma pigmentosum and trichothiodystrophy cells. Journal of molecular biology 33 7563073
2011 Polymorphisms in two DNA repair genes (XPD and XRCC1)--association with age related cataracts. Molecular vision 32 21245954
1984 Bloom's syndrome and EM9 cells in BrdU-containing medium exhibit similarly elevated frequencies of sister chromatid exchange but dissimilar amounts of cellular proliferation and chromosome disruption. Chromosoma 32 6510115
2003 DNA repair gene XPD and susceptibility to arsenic-induced hyperkeratosis. Toxicology letters 31 12749816
2008 Polymorphisms in XPC and ERCC2 genes, smoking and breast cancer risk. International journal of cancer 30 18196582
2008 XPD structure reveals its secrets. DNA repair 30 18692601
2019 XPD suppresses cell proliferation and migration via miR-29a-3p-Mdm2/PDGF-B axis in HCC. Cell & bioscience 28 30627419
2012 A polymorphism in the XPD gene predisposes to leukemic transformation and new nonmyeloid malignancies in essential thrombocythemia and polycythemia vera. Blood 28 22496165
1993 Cytogenetic effects of inhibition of topoisomerase I or II activities in the CHO mutant EM9 and its parental line AA8. Mutation research 27 7688089
1991 Repair of near-visible- and blue-light-induced DNA single-strand breaks by the CHO cell lines AA8 and EM9. Photochemistry and photobiology 26 1796118
2015 New mutation in the mouse Xpd/Ercc2 gene leads to recessive cataracts. PloS one 25 25951169
2011 Association of ERCC2/XPD polymorphisms and interaction with tobacco smoking in lung cancer susceptibility: a systemic review and meta-analysis. Molecular biology reports 25 21614524
2009 XPD polymorphisms, cigarette smoking, and bladder cancer risk: a meta-analysis. Journal of toxicology and environmental health. Part A 25 19492231
2017 Association between the ERCC2 Asp312Asn polymorphism and risk of cancer. Oncotarget 24 28489582
2023 NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression. Neoplasma 23 37498063
2014 Potentially functional polymorphisms in the ERCC2 gene and risk of esophageal squamous cell carcinoma in Chinese populations. Scientific reports 23 25209371
2014 Association between the XPD/ERCC2 Lys751Gln polymorphism and risk of cancer: evidence from 224 case-control studies. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 25113251
2013 XPD Asp312Asn and Lys751Gln polymorphisms and breast cancer susceptibility: a meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 22 24101192
2012 Abnormal XPD-induced nuclear receptor transactivation in DNA repair disorders: trichothiodystrophy and xeroderma pigmentosum. European journal of human genetics : EJHG 21 23232694
2009 Genetic polymorphisms in DNA repair gene APE1, XRCC1 and XPD and the risk of pre-eclampsia. European journal of obstetrics, gynecology, and reproductive biology 21 19592152
2009 Polymorphisms in the nucleotide excision repair gene ERCC2/XPD and risk of non-Hodgkin lymphoma. Cancer epidemiology 21 19736055
2011 Impact of DNA repair genes polymorphism (XPD and XRCC1) on the risk of breast cancer in Egyptian female patients. Molecular biology reports 20 21643959
1989 Mutagen-induced recombination between stably integrated neo gene fragments in CHO and EM9 cells. Mutation research 20 2716763
2022 Mechanism of lesion verification by the human XPD helicase in nucleotide excision repair. Nucleic acids research 18 35713557
2014 Association between DNA repair genes (XPD and XRCC1) polymorphisms and susceptibility to age-related cataract (ARC): a meta-analysis. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 18 24906341
2003 Insulin and glucose regulate the expression of the DNA repair enzyme XPD. Molecular and cellular endocrinology 18 12706296
2019 XPD/ERCC2 mutations interfere in cellular responses to oxidative stress. Mutagenesis 17 31348825
2013 ERCC1 and ERCC2 haplotype modulates induced BPDE-DNA adducts in primary cultured lymphocytes. PloS one 17 23593158
2012 Association between XPD Asp312Asn polymorphism and esophageal cancer susceptibility: a meta-analysis. Asian Pacific journal of cancer prevention : APJCP 17 22994751
2011 Association between XPD Lys751Gln polymorphism and risk of head and neck cancer: a meta-analysis. Genetics and molecular research : GMR 17 22179996
2009 Decreased expression and the Lys751Gln polymorphism of the XPD gene are associated with extreme longevity. Biogerontology 17 19707883
2005 Restoring DNA repair capacity of cells from three distinct diseases by XPD gene-recombinant adenovirus. Cancer gene therapy 17 15650764
1991 Characterization of revertants of the CHO EM9 mutant arising during DNA transfection. Carcinogenesis 17 2029744
2015 Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer. Cancer research and treatment 16 26130668
2010 The XPD helicase: XPanDing archaeal XPD structures to get a grip on human DNA repair. Biological chemistry 16 20482310
2005 Interethnic variability of ERCC2 polymorphisms. The pharmacogenomics journal 16 15534626

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