Affinage

XPA

DNA repair protein complementing XP-A cells · UniProt P23025

Length
273 aa
Mass
31.4 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 38 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XPA is a zinc-finger scaffold protein essential for nucleotide excision repair (NER), where it serves as a central hub coordinating damage verification and dual incision by recruiting and positioning TFIIH, RPA, and the ERCC1-XPF endonuclease on damaged DNA. XPA binds kinked or damaged DNA through a redefined DNA-binding domain (residues 98–239) containing a C4-type zinc finger (PMID:7526200, PMID:25056193), and cryo-EM structures show it inserts between the XPB and XPD subunits of TFIIH, kinking the duplex to orient the lesion-containing strand into XPD for verification (PMID:37076618). Two distinct interaction surfaces with RPA — an N-terminal disordered region contacting RPA32C and the DNA-binding domain contacting RPA70AB — organize the NER bubble into a U-shaped conformation that licenses dual incision, while a separate N-terminal peptide recruits ERCC1-XPF for 5′ incision (PMID:31925419, PMID:35969784, PMID:17948053). XPA levels are rate-limiting for NER and are regulated by HERC2-mediated ubiquitination counteracted by ATR phosphorylation at Ser196, by SIRT1-mediated deacetylation at Lys63/67 that enhances RPA binding, and by non-covalent PAR binding that modulates DNA affinity; loss of XPA causes PARP-1 hyperactivation and NAD+/SIRT1 depletion leading to defective mitophagy (PMID:21193487, PMID:23178497, PMID:20670893, PMID:24813611).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1991 Medium

    Establishing that XPA is a nuclear protein whose absence correlates with NER deficiency resolved the cellular compartment and confirmed the gene product as the functional entity lost in xeroderma pigmentosum group A.

    Evidence Immunoblotting and subcellular localization in normal and XP-A patient cells

    PMID:1918083

    Open questions at the time
    • Single antibody-based method; no functional rescue shown
  2. 1994 High

    Demonstrating that XPA is a zinc metalloprotein that preferentially binds damaged DNA through a C4-type zinc finger — and that zinc finger disruption abolishes both DNA binding and NER complementation — established that damage recognition depends on zinc-dependent protein folding.

    Evidence Filter binding, atomic absorption, CD spectroscopy, and Cys-103 mutagenesis with microinjection complementation

    PMID:7526200

    Open questions at the time
    • Mechanism of damage specificity versus normal DNA not resolved
    • No structural model at atomic resolution yet
  3. 1994 High

    Identifying XPA as a direct binding partner of ERCC1 and showing that XPA affinity-purified fractions contain ERCC1-XPF and complement multiple NER-deficient extracts established XPA as a scaffold recruiting the 5′ incision nuclease.

    Evidence Yeast two-hybrid, in vitro pulldown, XPA affinity chromatography with functional complementation

    PMID:8197174 PMID:8197175

    Open questions at the time
    • Precise binding interface not mapped
    • Whether interaction is direct in the context of chromatin unknown
  4. 1995 High

    Showing that XPA mutations abolishing ERCC1 binding prevent NER and act as dominant negatives proved the XPA–ERCC1 interaction is functionally required for the incision step, not merely correlated with it.

    Evidence Site-directed mutagenesis with in vitro repair synthesis and in vivo complementation

    PMID:7891694

    Open questions at the time
    • Structural basis of the interaction not yet determined
  5. 1996 High

    Mapping the minimal DNA-binding domain, defining the zinc coordination chemistry (Cys105/108/126/129), and showing sequential RPA then ERCC1 binding through non-overlapping XPA surfaces established the modular scaffold architecture of XPA.

    Evidence Domain truncation, ¹¹³Cd-NMR, surface plasmon resonance with quantitative KD measurements

    PMID:8538652 PMID:8972858 PMID:9078375

    Open questions at the time
    • Three-dimensional structure not yet solved
    • How DNA binding and partner binding are coordinated spatially unknown
  6. 1998 High

    The NMR solution structure of XPA's central domain revealed a zinc-containing subdomain and a positively charged cleft, mapping distinct surfaces for DNA and RPA binding and providing the first atomic-level framework for understanding XPA's dual recognition function.

    Evidence NMR spectroscopy with chemical shift perturbation mapping

    PMID:9699634

    Open questions at the time
    • Structure solved for isolated domain, not in complex with DNA or partners
    • Full-length structure unknown
  7. 1997 High

    Demonstrating that XPA directly recruits TFIIH to damage sites — TFIIH itself lacking damage preference — established XPA as the bridge between damage recognition and transcription factor-mediated DNA unwinding in NER.

    Evidence Filter binding and pulldown showing UV-damage-dependent TFIIH–XPA–DNA ternary complex

    PMID:9287294

    Open questions at the time
    • Which TFIIH subunit contacts XPA not identified
    • Structural basis unknown
  8. 2002 High

    Photo-crosslinking revealed that XPA contacts both damaged and undamaged strands while RPA preferentially binds the undamaged strand, establishing strand-specific roles for the XPA–RPA complex in NER bubble organization.

    Evidence Site-specific photoreactive crosslinking on cisplatin-damaged DNA

    PMID:11841234

    Open questions at the time
    • Whether this arrangement holds for all lesion types not tested
    • Dynamic strand exchange not addressed
  9. 2006 High

    Showing that XPA — but not XPC, CSB, XPF, or XPG — is required for ATR checkpoint activation after UV, and that ATR reciprocally controls XPA nuclear import, revealed a bidirectional regulatory loop between NER and checkpoint signaling.

    Evidence siRNA knockdown across multiple NER-mutant cell lines; Chk1/RPA phosphorylation; ATR-deficient cell analysis

    PMID:16675950 PMID:16862173

    Open questions at the time
    • Direct ATR phosphorylation site on XPA not yet identified in this study
    • Mechanism of ATRIP translocation dependence on XPA unclear
  10. 2007 High

    Crystal structures of ERCC1–XPA peptide and NMR of ERCC1 central domain defined the atomic-resolution interface, identified it as druggable, and showed ERCC1 simultaneously but non-competitively binds XPA and ssDNA.

    Evidence X-ray crystallography of ERCC1–XPA peptide; NMR of ERCC1 domain; peptide inhibition of cell-free NER

    PMID:17720715 PMID:17948053

    Open questions at the time
    • Full-length complex structure not available
    • In vivo druggability not demonstrated
  11. 2007 High

    Identifying DDB2 as a direct XPA-binding partner that stimulates CPD excision through residues 185–226 of XPA expanded XPA's scaffold role to include coupling UV-DDB damage recognition with downstream NER assembly.

    Evidence Co-IP, reconstituted NER with R207G mutant, immunofluorescence recruitment

    PMID:19056823

    Open questions at the time
    • Structural basis of DDB2–XPA interaction unknown
    • Whether this pathway operates on all GG-NER lesions unclear
  12. 2010 High

    Discovery that SIRT1 deacetylates XPA at Lys63/67 to enhance RPA binding, and that HERC2 ubiquitinates XPA for proteasomal degradation making XPA rate-limiting, established two major post-translational regulatory axes controlling NER capacity.

    Evidence In vitro deacetylation assays, Co-IP, UV sensitivity of acetylation-mimicking mutants; HERC2 ubiquitination assays and circadian regulation analysis

    PMID:20670893 PMID:21193487

    Open questions at the time
    • Whether acetylation and ubiquitination are coordinated unknown
    • Circadian regulation mechanism at the HERC2 level not resolved
  13. 2012 High

    Identifying ATR phosphorylation of XPA at Ser196 as the mechanism that stabilizes XPA by inhibiting HERC2-mediated ubiquitination closed the regulatory loop between DNA damage signaling and NER factor abundance.

    Evidence Phosphomimetic/phosphodeficient mutagenesis with Co-IP, ubiquitination assays, and chromatin fractionation

    PMID:23178497

    Open questions at the time
    • Whether other kinases phosphorylate Ser196 not tested
    • Kinetics of phosphorylation-dependent stabilization in vivo not determined
  14. 2014 High

    Demonstrating that XPA binds PAR non-covalently, stimulates PARP1 activity, and that XPA loss causes PARP1 hyperactivation leading to NAD+/SIRT1 depletion and defective mitophagy extended XPA's functional significance beyond NER to mitochondrial homeostasis.

    Evidence PAR-binding assays, PARP enzymatic assays, live-cell microirradiation, PINK1 cleavage and mitophagy assays, C. elegans lifespan rescue with NAD+ precursors

    PMID:24813611 PMID:24953096

    Open questions at the time
    • Whether PAR binding is the sole cause of mitochondrial phenotype not resolved
    • Direct mechanism linking XPA absence to PARP1 hyperactivation not established
  15. 2015 High

    Crystal structures of the yeast XPA ortholog Rad14 bound to cisplatin- and AAF-damaged DNA showed that two molecules bind and kink DNA by ~70°, providing the first structural framework for how XPA family proteins interrogate lesions.

    Evidence X-ray crystallography of Rad14–lesion–DNA complexes

    PMID:26100901

    Open questions at the time
    • Whether human XPA binds as a dimer on damage in vivo remains debated
    • Structures are of a yeast ortholog, not human XPA
  16. 2020 High

    NMR/SAXS mapping of both XPA–RPA interaction surfaces and demonstration that each is independently required for NER established the dual-contact model organizing the NER bubble into a U-shaped conformation.

    Evidence NMR, SAXS, mutagenesis with cellular and biochemical NER assays

    PMID:31925419 PMID:35969784

    Open questions at the time
    • Full atomic structure of the complete preincision complex not available at this stage
    • How the U-shape accommodates different lesion types unknown
  17. 2023 High

    Cryo-EM structures captured XPA positioned between XPB and XPD within TFIIH, showing it kinks the DNA duplex and shifts the lesion by nearly one helical turn to thread the damaged strand into XPD for verification — resolving how XPA integrates damage recognition with TFIIH-mediated scanning.

    Evidence Cryo-EM structural determination of NER preincision complexes at multiple stages

    PMID:37076618

    Open questions at the time
    • Transition states between scanning and incision not captured
    • How XPA dissociates after dual incision is unknown
    • Structures do not include ERCC1-XPF positioned for incision

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete structural model of the full NER preincision-to-incision transition — including simultaneous positioning of XPA, RPA, ERCC1-XPF, and XPG on a physiological lesion — and the mechanistic basis of XPA's role in PARP1-dependent mitochondrial homeostasis remain unresolved.
  • No structure of the complete dual-incision complex with all factors
  • Mechanism by which XPA absence causes PARP1 hyperactivation not established
  • Whether XPA dimerization is functionally relevant in vivo is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 7 GO:0060090 molecular adaptor activity 7 GO:0008289 lipid binding 1
Localization
GO:0005694 chromosome 2 GO:0005634 nucleus 1
Pathway
R-HSA-73894 DNA Repair 11 R-HSA-8953897 Cellular responses to stimuli 4
Partners
DDB2ERCC1PARP1PCNARPA1RPA2TFIIHXPF
Complex memberships
NER preincision complexXPA-RPA-ERCC1-XPF complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 XPA protein specifically interacts with ERCC1 both in vivo (yeast two-hybrid) and in vitro (recombinant proteins), and initial domain mapping identified regions in both proteins mediating the interaction, suggesting XPA recruits the ERCC1-containing incision complex to damage sites. Yeast two-hybrid system; in vitro pulldown with recombinant proteins Proceedings of the National Academy of Sciences of the United States of America High 8197174
1994 XPA protein forms a ternary complex with ERCC1 and ERCC4(XPF) heterodimer; an XPA affinity column depleted excision repair activity from HeLa extracts, and the XPA-bound fraction complemented ERCC1, XPF, and XPA mutant extracts. XPA affinity column chromatography; in vitro complementation assay Proceedings of the National Academy of Sciences of the United States of America High 8197175
1995 Mutations in XPA that abolish ERCC1 binding (deletion of G motif or E motif) prevent complementation of NER-deficient cells; the delta-G mutant acts as a dominant negative in wild-type extracts, establishing that XPA-ERCC1 interaction is required for the incision step of NER. Site-directed mutagenesis; in vitro DNA repair synthesis assay; in vivo complementation Molecular and cellular biology High 7891694
1994 XPA is a zinc metalloprotein that binds preferentially to UV-, cisplatin-, or OsO4-damaged DNA; mutation of Cys-103 in the C4-type zinc finger abolishes both DNA-binding and XP-A correcting activity, establishing the zinc finger as essential for protein conformation and function. Nitrocellulose filter binding assay; atomic absorption; UV-CD spectra; site-directed mutagenesis; microinjection complementation assay Mutation research High 7526200
1996 The minimal DNA-binding domain of XPA was mapped to a 122-amino-acid region (MF122) containing the C4-type zinc finger motif, which is sufficient for preferential binding to UV- or cisplatin-damaged DNA. Truncation analysis; nitrocellulose filter binding assay; CD spectroscopy Mutation research High 8538652
1996 The DNA-binding domain of XPA contains one zinc ion coordinated by four cysteine residues (Cys105, Cys108, Cys126, Cys129) forming a Cys-X2-Cys-X17-Cys-X2-Cys motif essential for protein folding, as shown by 113Cd-NMR combined with atomic absorption and site-directed mutagenesis. 113Cd-NMR; atomic absorption spectroscopy; site-directed mutagenesis Genes to cells High 9078375
1996 Sequential binding of RPA and ERCC1 to XPA occurs through non-overlapping regions; RPA 70 kDa subunit binds the middle region of XPA, RPA 34 kDa subunit binds the N-terminal region, and ERCC1 binds a distinct region; a ternary RPA-XPA-ERCC1 complex is detectable in vitro. Dissociation constants were determined (RPA KD ~19 nM; ERCC1 KD ~250 nM), with RPA binding first facilitating ERCC1 binding. Surface plasmon resonance; in vitro pulldown; domain mapping Nucleic acids research High 8972858
1998 NMR solution structure of the central domain of XPA (residues 98-219) revealed a zinc-containing subdomain and a C-terminal alpha/beta subdomain with a positively charged cleft; NMR mapping identified distinct surfaces on the domain for DNA binding and RPA binding. NMR spectroscopy Nature structural biology High 9699634
1997 XPA recruits TFIIH to DNA damage sites through direct protein-protein interaction; TFIIH lacks intrinsic preference for UV-damaged DNA but binds XPA-DNA complexes in a UV damage-dependent manner via a direct protein-protein interaction with XPA. Filter binding assay; pulldown experiments The Journal of biological chemistry High 9287294
2000 RPA32 C-terminal domain contains a specific surface that interacts with XPA (as well as UNG2 and RAD52) in a similar structural manner; NMR structures of RPA32C domain free and in complex with UNG2 defined the common binding interface, supporting a hand-off model for assembly of different DNA repair complexes. NMR structure determination; protein interaction mapping Cell High 11081631
2007 Crystal structure of ERCC1 in complex with an XPA peptide showed that only a small region of XPA (within the N-terminal domain) interacts with ERCC1 with submicromolar affinity; this peptide potently inhibits NER activity in a cell-free cisplatin excision assay, identifying the XPA-ERCC1 interface as a druggable target. X-ray crystallography; cell-free NER assay with peptide inhibitor The EMBO journal High 17948053
2009 ERCC1 residues Asn-110 and Tyr-145 are critical for XPA binding; mutation of these residues abolishes XPA interaction and prevents ERCC1-XPF recruitment to UV damage sites, severely impairs (6-4)PP repair and causes UV hypersensitivity, but does not affect nuclease activity on model substrates or rescue of sensitivity to crosslinking agents. Site-directed mutagenesis; immunofluorescence; cell-based repair assays; UV sensitivity assay The Journal of biological chemistry High 19940136
2010 SIRT1 deacetylates XPA at lysines 63 and 67 both in vitro and in cells; interaction between SIRT1 and XPA is enhanced after UV irradiation; cells expressing hyperacetylation-mimicking XPA-K63,67Q show increased UV sensitivity; SIRT1-mediated XPA deacetylation enhances XPA's interaction with RPA32, linking SIRT1-regulated acetylation to NER activity. In vitro deacetylation assay; Co-IP; UV sensitivity assay; site-directed mutagenesis Molecular cell High 20670893
2010 XPA is a rate-limiting factor in NER in all human cell lines tested; its level is regulated at the transcriptional level by the circadian clock and post-translationally by the HECT E3 ubiquitin ligase HERC2, which ubiquitinates and degrades XPA; DNA damage promotes XPA-chromatin association and dissociation from HERC2, stabilizing XPA. siRNA knockdown; protein level quantification; ubiquitination assay; circadian regulation analysis Nucleic acids research High 21193487
2012 ATR phosphorylates XPA at Ser196 upon UV damage, enhancing XPA stability by inhibiting HERC2-mediated ubiquitination and degradation; phosphomimetic S196D shows delayed degradation and reduced HERC2 binding, while phosphodeficient S196A shows persistent HERC2 association and increased ubiquitination; ATR also enhances XPA chromatin retention and interaction with binding partners. Phosphomimetic/phosphodeficient mutagenesis; Co-IP; ubiquitination assay; chromatin fractionation Oncogene High 23178497
2000 XAB1, a novel cytoplasmic GTPase, binds the N-terminal region of XPA (residues 30-34 required); deletion of the nuclear localization signal-containing region of XPA abolishes XAB1 interaction; XAB1 is predominantly cytoplasmic and has intrinsic GTPase activity, suggesting a role in XPA nuclear localization. Yeast two-hybrid; recombinant protein assay; immunofluorescence; GTPase activity assay Nucleic acids research Medium 11058119
2006 XPA is required for ATR checkpoint signaling in S-phase after UV irradiation; XPA-deficient cells show defective ATRIP translocation to UV damage sites, reduced UV-induced Chk1 phosphorylation, and reduced RPA phosphorylation and chromatin binding, while XPC, CSB, XPF, and XPG-deficient cells do not, indicating that XPA's lesion recognition function (not NER per se) triggers ATR activation. siRNA knockdown; immunofluorescence; western blot phosphorylation analysis; comparison across NER-mutant cell lines The EMBO journal High 16675950
2006 ATR kinase activity is required for UV-induced nuclear accumulation and focus formation of XPA; ATR-deficient cells lack UV-induced XPA nuclear translocation while ATM-deficient cells retain it; siRNA against ATR or kinase inhibitor treatment compromises UV-induced XPA nuclear import. siRNA knockdown; kinase inhibition; immunofluorescence; cell fractionation Oncogene High 16862173
2013 UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner; importin-α4 and importin-α7 directly interact with XPA; importin-α4 binding is UV-damage dependent, while importin-α7 binding is constitutive; siRNA knockdown of XAB1 did not affect nuclear XPA import. Co-IP; siRNA knockdown; immunofluorescence; nuclear fractionation PloS one Medium 23861882
2002 XPA forms a homodimer (XPA2) in solution under normal conditions; XPA2 (not monomer) forms the complex with RPA; XPA dimerization is not due to disulfide bonds and is stable over a broad range of concentrations, suggesting dimerization may be important for DNA damage recognition. Native gel filtration chromatography; native PFO-PAGE; fluorescence spectroscopy; mass spectrometry Biochemistry Medium 12390028
2002 Both RPA and XPA contact the cisplatin adduct in damaged DNA; XPA contacts both the damaged and undamaged strands; RPA preferentially binds the undamaged strand, as determined by site-specific photo-crosslinking. Site-specific photoreactive crosslinking; protein-DNA interaction mapping Biochemistry High 11841234
2007 DDB (primarily through DDB2 subunit) directly interacts with XPA; XPA residues 185-226 are important for interaction; the XP-A revertant mutation R207G reduces DDB-XPA interaction both in vitro and in vivo; in a reconstituted system, DDB fails to stimulate CPD excision with R207G-XPA; R207G-XPA shows reduced recruitment to DNA damage sites and fails to support DDB2-enhanced CPD repair. Co-IP; in vitro interaction assay; reconstituted NER assay; immunofluorescence recruitment assay Nucleic acids research High 19056823
2014 XPA binds PAR (poly-ADP-ribose) non-covalently through specific basic amino acids in a conserved PAR-binding motif overlapping the DDB2 and TFIIH interaction domains; XPA-PAR interaction lowers XPA's DNA-binding affinity; XPA itself strongly stimulates PARP1 enzymatic activity; PARP inhibition impairs NER and alters XPA recruitment kinetics to laser-induced damage sites. Biochemical PAR-binding assay; mutagenesis; PARP enzymatic assay; live-cell microirradiation/fluorescence The FEBS journal High 24953096
2014 XPA-deficient cells show defective mitophagy with excessive PINK1 cleavage and increased mitochondrial membrane potential, caused by decreased activation of the NAD+/SIRT1/PGC-1α axis triggered by PARP-1 hyperactivation; PARP-1 inhibition or NAD+ precursor supplementation rescues these mitochondrial abnormalities and lifespan defect in xpa-1 nematodes. Cell-based mitophagy assays; PINK1 cleavage assay; PARP-1 inhibition; NAD+ supplementation; nematode lifespan assay Cell High 24813611
2015 Crystal structures of the yeast XPA homolog Rad14 DNA-binding domain bound to DNA with cisplatin (1,2-GG) or AAF-dG lesions showed that two Rad14 molecules bind the duplex, each interrogating it with a β-hairpin and inducing a 70° DNA kink at the lesion; DNA melting occurs remote from the lesion; the covalent fixation of crosslinked bases or AAF intercalation stabilizes the kinked structure. X-ray crystallography Proceedings of the National Academy of Sciences of the United States of America High 26100901
2020 Two interaction surfaces between XPA and RPA organize the NER preincision complex: (1) XPA N-terminal disordered domain with RPA32C domain, and (2) XPA DNA-binding domain with RPA70AB tandem domains; NMR mapping and SAXS combined with docking revealed XPA and RPA orientation on model NER DNA substrates; XPA mutations inhibiting RPA70AB interaction decrease NER activity in cellular assays; the two ss/dsDNA junctions of the NER bubble must adopt a U-shape with junctions in close proximity. NMR; X-ray scattering (SAXS); mutagenesis; cell-based NER assay Nucleic acids research High 31925419
2022 Both XPA-RPA interaction surfaces (XPA-N/RPA32C and XPA-DBD/RPA70AB) are functionally required for NER; mutations in either site reduce NER activity and combined mutations cause additive inhibition; XPA-N/RPA32C interaction is important for initial XPA recruitment to NER complexes, while XPA-DBD/RPA70AB interaction organizes the complex to license dual incision; integrative structural models suggest the NER bubble adopts a U-shaped conformation. Mutagenesis; biochemical NER assay; cellular NER assay; integrative structural modeling Proceedings of the National Academy of Sciences of the United States of America High 35969784
2023 Cryo-EM structures revealed that XPA binds between XPB and XPD within the NER preincision complex; XPA kinks the DNA duplex and shifts XPC and the DNA lesion by nearly one helical turn relative to the TFIIH Core7, positioning the lesion outside Core7 where XPD can verify it by threading the lesion-containing strand. Cryo-EM structural determination Nature High 37076618
2012 XPA contains a functional APIM (AlkB homolog 2 PCNA-interacting motif) that mediates interaction with PCNA; XPA co-localizes with PCNA at replication foci in undamaged cells; APIM-mutant XPA fails to fully complement UV sensitivity and CPD/(6-4)PP repair in XPA-deficient cells, establishing a PCNA interaction-dependent NER role near the replisome. In vivo PCNA interaction assay; live-cell imaging (colocalization); UV sensitivity assay; CPD/6-4PP repair assay PloS one Medium 23152873
2014 The XPA DNA-binding domain should be redefined as residues 98-239 rather than 98-219; XPA(98-239) binds Y-shaped ssDNA-dsDNA junction substrates with the same affinity as full-length XPA, while XPA(98-219) binds with substantially weaker affinity; NMR showed XPA(98-239) has the same globular core as XPA(98-219) and may undergo conformational change upon DNA binding. Fluorescence anisotropy DNA-binding assay; NMR; domain truncation analysis Journal of the American Chemical Society High 25056193
2007 Solution structure of the ERCC1 central domain revealed structural homology to the XPF nuclease domain, but functional analysis shows it has distinct function: mediating interactions with both XPA and single-stranded DNA through non-competitive, distinct surfaces that can bind simultaneously. NMR structure; functional interaction mapping Nucleic acids research High 17720715
2017 MMSET (methyltransferase), recruited to DNA damage sites by DICER, catalyzes dimethylation of histone H4 at lysine 20 (H4K20me2) at UV damage sites; this H4K20me2 mark facilitates XPA recruitment to damage sites in the global-genomic NER branch. ChIP; siRNA knockdown; immunofluorescence; histone methylation assay The Journal of cell biology Medium 29233865
2007 XPA mis-localizes to DNA double-strand break (DSB) sites in Hutchinson-Gilford progeria syndrome (HGPS) and Zmpste24-deficient cells (which accumulate progerin/prelamin A); XPA-DSB association is mediated by DNA (shown by ChIP and Co-IP); RNAi knockdown of XPA in HGPS cells partially restores DSB repair, indicating XPA mislocalization inhibits DSB repair. Immunofluorescence; modified ChIP; Co-immunoprecipitation; RNAi knockdown; comet assay FASEB journal Medium 17848622
2014 RASSF1A forms a DNA damage-regulated complex with XPA, is required for full XPA repair activity; RASSF1A-deficient cells have impaired NER; RASSF1A and a cancer-associated SNP variant differentially regulate XPA acetylation status and the XPA-RPA70 interaction, with the SNP variant hyperstabilizing the XPA-RPA70 complex. Co-IP; NER functional assay; RASSF1A knockdown/overexpression; acetylation analysis Molecular and cellular biology Medium 25368379
2015 HMGB1 and XPA co-dependently recruit each other to triplex-directed psoralen ICL sites; HMGB1 depletion in XPA-deficient cells alters ICL-induced mutation spectrum; HMGB1 introduces negative supercoils in ICL-containing plasmids in HeLa cell extracts, suggesting it facilitates an architectural environment for XPA-dependent ICL repair. Co-IP; siRNA knockdown; mutation analysis; in vitro supercoiling assay Nucleic acids research Medium 26578599
2000 Toxic metal compounds (Cd(II), Co(II), Ni(II), Cu(II)) inhibit XPA DNA-binding activity by targeting its zinc finger domain; simultaneous treatment with Zn(II) prevents this inhibition for Cd(II), Co(II), and Ni(II) but not fully for Cu(II); Hg(II), Pb(II), and As(III) do not diminish XPA DNA binding. In vitro DNA binding assay with UV-irradiated oligonucleotide; zinc competition experiments Carcinogenesis Medium 11062174
2003 Ni(II) forms a square planar complex with the XPA zinc finger peptide (XPAzf), displacing Zn(II) and disrupting the native tetrahedral zinc coordination; Ni(II)-substituted XPAzf loses its overall zinc finger structure; Zn(II)-saturated XPAzf is resistant to oxidation but Ni(II) accelerates oxidative damage in the presence of H2O2. Fluorescence spectroscopy; UV-vis; CD spectroscopy; HPLC oxidation analysis Chemical research in toxicology Medium 12588196
1991 XPA protein is localized in the nucleus of normal human cells; absence of XPA protein correlates with the degree of repair deficiency in XP-A cells. Immunoblotting with anti-XPA antibody; subcellular localization by antibody detection The Journal of biological chemistry Medium 1918083

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell 565 24813611
1994 Messenger RNA levels of XPAC and ERCC1 in ovarian cancer tissue correlate with response to platinum-based chemotherapy. The Journal of clinical investigation 380 8040325
1994 Specific association between the human DNA repair proteins XPA and ERCC1. Proceedings of the National Academy of Sciences of the United States of America 278 8197174
2000 Structural basis for the recognition of DNA repair proteins UNG2, XPA, and RAD52 by replication factor RPA. Cell 214 11081631
2010 SIRT1 regulates UV-induced DNA repair through deacetylating XPA. Molecular cell 184 20670893
1994 Formation of a ternary complex by human XPA, ERCC1, and ERCC4(XPF) excision repair proteins. Proceedings of the National Academy of Sciences of the United States of America 183 8197175
2000 Differential effects of toxic metal compounds on the activities of Fpg and XPA, two zinc finger proteins involved in DNA repair. Carcinogenesis 154 11062174
2003 XPA polymorphism associated with reduced lung cancer risk and a modulating effect on nucleotide excision repair capacity. Carcinogenesis 141 12663511
1994 The XPA protein is a zinc metalloprotein with an ability to recognize various kinds of DNA damage. Mutation research 137 7526200
1997 A sequence in the N-terminal region of human uracil-DNA glycosylase with homology to XPA interacts with the C-terminal part of the 34-kDa subunit of replication protein A. The Journal of biological chemistry 134 9045683
2007 Structural basis for the recruitment of ERCC1-XPF to nucleotide excision repair complexes by XPA. The EMBO journal 129 17948053
1998 Solution structure of the DNA- and RPA-binding domain of the human repair factor XPA. Nature structural biology 123 9699634
2003 Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice. DNA repair 116 12509265
1995 Mutations in XPA that prevent association with ERCC1 are defective in nucleotide excision repair. Molecular and cellular biology 113 7891694
2001 Aberrant mobility phenomena of the DNA repair protein XPA. Protein science : a publication of the Protein Society 106 11420437
2003 Critical DNA damage recognition functions of XPC-hHR23B and XPA-RPA in nucleotide excision repair. Molecular carcinogenesis 102 12949838
2010 Regulation of nucleotide excision repair activity by transcriptional and post-transcriptional control of the XPA protein. Nucleic acids research 101 21193487
2002 Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions. Proceedings of the National Academy of Sciences of the United States of America 98 11972036
2001 Triplex-induced recombination in human cell-free extracts. Dependence on XPA and HsRad51. The Journal of biological chemistry 97 11278954
1997 DNA damage recognition by XPA protein promotes efficient recruitment of transcription factor II H. The Journal of biological chemistry 96 9287294
2007 Involvement of xeroderma pigmentosum group A (XPA) in progeria arising from defective maturation of prelamin A. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 92 17848622
2009 The XPA-binding domain of ERCC1 is required for nucleotide excision repair but not other DNA repair pathways. The Journal of biological chemistry 91 19940136
1996 Identification of a damaged-DNA binding domain of the XPA protein. Mutation research 91 8538652
1996 Sequential binding of DNA repair proteins RPA and ERCC1 to XPA in vitro. Nucleic acids research 84 8972858
2006 Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase eta on ATR checkpoint signaling. The EMBO journal 80 16675950
2006 ATR-dependent checkpoint modulates XPA nuclear import in response to UV irradiation. Oncogene 77 16862173
2006 XPA protein as a limiting factor for nucleotide excision repair and UV sensitivity in human cells. DNA repair 73 16413230
1992 Identification of splicing mutations of the last nucleotides of exons, a nonsense mutation, and a missense mutation of the XPAC gene as causes of group A xeroderma pigmentosum. Mutation research 72 1372103
1996 Enhanced inflammation and immunosuppression by ultraviolet radiation in xeroderma pigmentosum group A (XPA) model mice. The Journal of investigative dermatology 71 8751968
2003 Mechanism of nickel assault on the zinc finger of DNA repair protein XPA. Chemical research in toxicology 67 12588196
2008 Alterations in candidate genes PHF2, FANCC, PTCH1 and XPA at chromosomal 9q22.3 region: pathological significance in early- and late-onset breast carcinoma. Molecular cancer 66 18990233
1997 Spontaneous liver tumors and benzo[a]pyrene-induced lymphomas in XPA-deficient mice. Molecular carcinogenesis 66 9180928
1998 Structural features of the minimal DNA binding domain (M98-F219) of human nucleotide excision repair protein XPA. Nucleic acids research 65 9592168
2023 Lesion recognition by XPC, TFIIH and XPA in DNA excision repair. Nature 60 37076618
2014 Poly(ADP-ribose)-mediated interplay of XPA and PARP1 leads to reciprocal regulation of protein function. The FEBS journal 59 24953096
2012 Nucleotide excision repair is associated with the replisome and its efficiency depends on a direct interaction between XPA and PCNA. PloS one 58 23152873
2012 Virtual screening and biological evaluation of inhibitors targeting the XPA-ERCC1 interaction. PloS one 57 23272099
2005 Human XPC-hHR23B interacts with XPA-RPA in the recognition of triplex-directed psoralen DNA interstrand crosslinks. Nucleic acids research 57 15914671
2012 Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair. Oncogene 56 23178497
2002 Dimerization of human XPA and formation of XPA2-RPA protein complex. Biochemistry 56 12390028
2012 HIF1α regulated expression of XPA contributes to cisplatin resistance in lung cancer. Carcinogenesis 54 22467238
2006 Possible involvement of XPA in repair of oxidative DNA damage deduced from analysis of damage, repair and genotype in a human population study. Mutagenesis 54 16613913
2020 XPA: DNA Repair Protein of Significant Clinical Importance. International journal of molecular sciences 53 32235701
1995 Overexpression of the XPA repair gene increases resistance to ultraviolet radiation in human cells by selective repair of DNA damage. Cancer research 53 8521407
2002 Strand-specific binding of RPA and XPA to damaged duplex DNA. Biochemistry 52 11841234
1993 High prevalence of the point mutation in exon 6 of the xeroderma pigmentosum group A-complementing (XPAC) gene in xeroderma pigmentosum group A patients in Tunisia. American journal of human genetics 52 8105686
2001 Binding of XPA and RPA to damaged DNA investigated by fluorescence anisotropy. Biochemistry 50 11258902
2000 A novel cytoplasmic GTPase XAB1 interacts with DNA repair protein XPA. Nucleic acids research 49 11058119
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2004 Association between the risk for lung adenocarcinoma and a (-4) G-to-A polymorphism in the XPA gene. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 45 15598786
2001 DNA repair-deficient Xpa and Xpa/p53+/- knock-out mice: nature of the models. Toxicologic pathology 43 11695546
1998 Mutational analysis of a function of xeroderma pigmentosum group A (XPA) protein in strand-specific DNA repair. Nucleic acids research 43 9753735
1992 Molecular basis of group A xeroderma pigmentosum: a missense mutation and two deletions located in a zinc finger consensus sequence of the XPAC gene. Human genetics 43 1339397
2020 A key interaction with RPA orients XPA in NER complexes. Nucleic acids research 42 31925419
1998 Differential expression of the TFF-peptides xP1 and xP4 in the gastrointestinal tract of Xenopus laevis. Cell and tissue research 42 9394039
2017 Progerin sequestration of PCNA promotes replication fork collapse and mislocalization of XPA in laminopathy-related progeroid syndromes. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39 28515154
2015 TP53 mutations induced by BPDE in Xpa-WT and Xpa-Null human TP53 knock-in (Hupki) mouse embryo fibroblasts. Mutation research 39 25847421
2000 Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population. Human mutation 39 10862089
2015 Role of the XPA protein in the NER pathway: A perspective on the function of structural disorder in macromolecular assembly. Computational and structural biotechnology journal 38 26865925
2007 Analysis of the XPA and ssDNA-binding surfaces on the central domain of human ERCC1 reveals evidence for subfunctionalization. Nucleic acids research 38 17720715
2007 The ING1b tumor suppressor facilitates nucleotide excision repair by promoting chromatin accessibility to XPA. Experimental cell research 37 17379210
2015 Structural insights into the recognition of cisplatin and AAF-dG lesion by Rad14 (XPA). Proceedings of the National Academy of Sciences of the United States of America 36 26100901
2014 Redefining the DNA-binding domain of human XPA. Journal of the American Chemical Society 36 25056193
2002 The Caenorhabditis elegans XPA homolog of human XPA. Molecules and cells 36 12243352
2000 Mutagenesis and carcinogenesis in nucleotide excision repair-deficient XPA knock out mice. Mutation research 35 10838141
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2014 The RASSF1A tumor suppressor regulates XPA-mediated DNA repair. Molecular and cellular biology 33 25368379
2009 Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5'-GTgG-3' sequence: destabilization of two base pairs at the lesion site. Nucleic acids research 32 19892827
2008 Physical and functional interaction between DDB and XPA in nucleotide excision repair. Nucleic acids research 31 19056823
2005 Severe growth retardation and short life span of double-mutant mice lacking Xpa and exon 15 of Xpg. DNA repair 31 15661658
2002 Low amounts of the DNA repair XPA protein are sufficient to recover UV-resistance. Carcinogenesis 31 12082027
2022 Two interaction surfaces between XPA and RPA organize the preincision complex in nucleotide excision repair. Proceedings of the National Academy of Sciences of the United States of America 30 35969784
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2020 Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours. BMC cancer 29 31906898
2010 Antimony impairs nucleotide excision repair: XPA and XPE as potential molecular targets. Chemical research in toxicology 29 20509621
2006 Induction of nevi and skin tumors in Ink4a/Arf Xpa knockout mice by neonatal, intermittent, or chronic UVB exposures. Cancer research 29 16510579
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2017 CXCL1 Inhibition Regulates UVB-Induced Skin Inflammation and Tumorigenesis in Xpa-Deficient Mice. The Journal of investigative dermatology 28 28528167
2001 Intestinal toxicity and carcinogenic potential of the food mutagen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in DNA repair deficient XPA-/- mice. Carcinogenesis 28 11285198
2001 DMBA-induced toxic and mutagenic responses vary dramatically between NER-deficient Xpa, Xpc and Csb mice. Carcinogenesis 28 11408355
1991 Molecular cloning of human XPAC gene homologs from chicken, Xenopus laevis and Drosophila melanogaster. Biochemical and biophysical research communications 28 1764072
2008 XPA gene, its product and biological roles. Advances in experimental medicine and biology 27 19181108
1999 Effect of heterozygous loss of p53 on benzo[a]pyrene-induced mutations and tumors in DNA repair-deficient XPA mice. Environmental and molecular mutagenesis 27 10529736
2002 Additive roles of XPA and MSH2 genes in UVB-induced skin tumorigenesis in mice. DNA repair 26 12531021
2000 Overexpression and purification of human XPA using a baculovirus expression system. Protein expression and purification 26 10833384
2013 UV-induced nuclear import of XPA is mediated by importin-α4 in an ATR-dependent manner. PloS one 25 23861882
2007 Crosslinking of the NER damage recognition proteins XPC-HR23B, XPA and RPA to photoreactive probes that mimic DNA damages. Biochimica et biophysica acta 25 17320292
2001 UV-induced skin carcinogenesis in xeroderma pigmentosum group A (XPA) gene-knockout mice with nucleotide excision repair-deficiency. Mutation research 25 11376684
2010 XPA impacts formation but not proteasome-sensitive repair of DNA-protein cross-links induced by chromate. Mutagenesis 24 20410141
2010 XPA gene mutations resulting in subtle truncation of protein in xeroderma pigmentosum group A patients with mild skin symptoms. The Journal of investigative dermatology 24 20574439
2008 Elevation of XPA protein level in testis tumor cells without increasing resistance to cisplatin or UV radiation. Molecular carcinogenesis 24 18240296
2008 Interaction of nucleotide excision repair factors XPC-HR23B, XPA, and RPA with damaged DNA. Biochemistry. Biokhimiia 24 18774935
2007 Domains in the XPA protein important in its role as a processivity factor. Biochemical and biophysical research communications 24 17349973
2017 Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue. Toxicology and applied pharmacology 23 28552776
2017 DICER- and MMSET-catalyzed H4K20me2 recruits the nucleotide excision repair factor XPA to DNA damage sites. The Journal of cell biology 23 29233865
2015 HMGB1 interacts with XPA to facilitate the processing of DNA interstrand crosslinks in human cells. Nucleic acids research 23 26578599
2013 The broccoli-born isothiocyanate sulforaphane impairs nucleotide excision repair: XPA as one potential target. Archives of toxicology 23 24352536
2001 Differential ultraviolet-B-induced immunomodulation in XPA, XPC, and CSB DNA repair-deficient mice. The Journal of investigative dermatology 23 11442761
1998 Use of DNA repair-deficient XPA transgenic mice in short-term carcinogenicity testing. Toxicologic pathology 23 9864090
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