Affinage

XRCC1

DNA repair protein XRCC1 · UniProt P18887

Round 2 corrected
Length
633 aa
Mass
69.5 kDa
Annotated
2026-04-28
130 papers in source corpus 26 papers cited in narrative 26 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XRCC1 is a scaffold protein that coordinates DNA single-strand break repair (SSBR) and base excision repair (BER) by assembling multi-enzyme repair complexes at sites of DNA damage. Its N-terminal domain binds DNA polymerase β (residues 84–183), its central BRCT1 domain binds poly(ADP-ribose) synthesized by PARP1/PARP2 to mediate damage-site recruitment, and its C-terminal region binds DNA ligase IIIα; it also stimulates the enzymatic activities of polynucleotide kinase and APE1, with its protein stability regulated by CK2 phosphorylation and SIRT1-mediated deacetylation that prevents β-TrCP ubiquitination (PMID:8978692, PMID:26130715, PMID:11163244, PMID:11707423, PMID:20471329, PMID:31043584). A critical function of XRCC1 is to act as an anti-trapper that prevents toxic PARP1 engagement on BER intermediates; loss of XRCC1 causes PARP1 hyperactivation leading to transcriptional suppression via USP3-mediated histone de-ubiquitination, NAD+ depletion, and neurodegeneration that is rescued by PARP1 deletion (PMID:34102106, PMID:34811483, PMID:35778544). Biallelic loss-of-function mutations in human XRCC1 cause ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia driven by PARP1 hyperactivation (PMID:28002403).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1990 High

    Cloning XRCC1 established it as a gene essential for single-strand break repair, resolving the molecular identity behind the radiation-sensitive CHO EM9 complementation group and linking it to alkylating-agent sensitivity and elevated sister chromatid exchange.

    Evidence cDNA cloning and functional complementation of CHO EM9 cells with strand-break repair kinetics, SCE, and survival assays

    PMID:2247054

    Open questions at the time
    • No catalytic activity or interaction partners identified
    • Mechanism of XRCC1 action in repair unknown
  2. 1996 High

    Identification of DNA ligase III and DNA polymerase β as direct XRCC1 partners, with domain mapping, established that XRCC1 is a non-catalytic scaffold that coordinates the ligation and gap-filling steps of BER.

    Evidence BER reconstitution with purified proteins, far Western blotting, yeast two-hybrid, and affinity precipitation with domain fragments

    PMID:8264637 PMID:8978692 PMID:9136882

    Open questions at the time
    • No information on how XRCC1 is recruited to damage sites
    • Role of other potential partners unexplored
  3. 1998 High

    Discovery that XRCC1 physically associates with PARP-1 via its BRCT1 domain and negatively regulates PARP-1 activity revealed a regulatory link between damage sensing and scaffold-mediated repair assembly.

    Evidence Yeast two-hybrid, co-immunoprecipitation, and PARP-1 activity assay after XRCC1 overexpression

    PMID:9584196

    Open questions at the time
    • Whether PARP-1 activity is required for XRCC1 recruitment not yet tested
    • PARP-2 relationship unknown
  4. 2001 High

    Expansion of the XRCC1 interactome to include PNK and APE1, with demonstration that XRCC1 stimulates their enzymatic activities, established XRCC1 as a hub that accelerates multiple enzymatic steps in SSBR beyond ligation.

    Evidence Co-immunoprecipitation, in vitro kinase/phosphatase and endonuclease activity assays, cellular complementation of XRCC1-deficient cells

    PMID:11163244 PMID:11707423

    Open questions at the time
    • Structural basis for enzymatic stimulation unknown
    • Relative contributions of each interaction to overall repair rate not quantified
  5. 2003 High

    Demonstration that PARP-1-generated poly(ADP-ribose) is required for XRCC1 nuclear focus formation answered how XRCC1 is recruited to damage sites, placing PAR as the upstream signal.

    Evidence Immunofluorescence of XRCC1 foci in PARP-1 KO MEFs and BRCT1 mutants after H₂O₂

    PMID:14500814

    Open questions at the time
    • PARP-2 redundancy not tested
    • Whether PAR binding is direct via BRCT1 or indirect not resolved
  6. 2005 High

    Systematic biochemical dissection showed the primary defect in XRCC1-deficient cells is impaired nick ligation rather than base excision or gap filling, pinpointing the rate-limiting step controlled by XRCC1.

    Evidence Whole-cell extract BER/SSBR assays across multiple substrates in EM9 cells

    PMID:16245950

    Open questions at the time
    • Whether this reflects ligase III stabilization or direct ligation stimulation not distinguished
  7. 2010 High

    Identification of CK2 as the kinase that phosphorylates XRCC1 to stabilize the XRCC1–ligase IIIα complex provided the first post-translational regulatory mechanism controlling XRCC1 protein levels and repair capacity.

    Evidence Kinase activity screen in cell extracts, CK2 siRNA, phosphosite mutants, co-immunoprecipitation, comet assay

    PMID:20471329

    Open questions at the time
    • Other kinases or phosphatases that modulate XRCC1 not explored
    • CK2 regulation in response to damage not characterized
  8. 2015 High

    Direct PAR binding by the XRCC1 BRCT1 phosphate-binding pocket was shown to be necessary for PARP-1 interaction, damage recruitment, and repair acceleration, resolving that XRCC1 senses PAR through its BRCT1 domain rather than through protein–protein contact with PARP-1.

    Evidence PAR-binding assays with BRCT1 mutants, PARP-1 co-IP, live-cell damage recruitment, BER/SSBR and clonogenic assays

    PMID:26130715

    Open questions at the time
    • Structural details of BRCT1–PAR interaction at atomic resolution not available
  9. 2016 High

    Human XRCC1 biallelic loss-of-function mutations were linked to cerebellar ataxia and neurodegeneration, and genetic rescue by PARP1 deletion in mice identified PARP1 hyperactivation as the pathogenic driver, transforming understanding from a DNA repair deficiency model to one of toxic PARP1 signaling.

    Evidence Patient fibroblast SSBR/PAR assays, Xrcc1/Parp1 double-KO mouse with cerebellar neuron counts and ADP-ribosylation quantification

    PMID:28002403

    Open questions at the time
    • Downstream effectors of toxic PARylation in neurons not fully delineated
    • Whether other tissues are similarly affected by PARP hyperactivation unknown
  10. 2017 High

    Establishing that PARP1 and PARP2 are redundant for XRCC1 recruitment explained why single PARP KOs show mild repair phenotypes, requiring loss of both PARPs to ablate XRCC1 chromatin binding.

    Evidence Isogenic PARP1/PARP2 single and double KO human cells with chromatin fractionation after H₂O₂

    PMID:27965414

    Open questions at the time
    • Whether PARP3 contributes under specific damage contexts not fully excluded
  11. 2019 High

    Discovery that SIRT1-mediated deacetylation protects XRCC1 from β-TrCP-dependent ubiquitination and degradation identified a second post-translational axis (acetylation/ubiquitination) controlling XRCC1 stability, complementing the CK2 phosphorylation mechanism.

    Evidence Site-directed mutagenesis of K260/K298/K431, ubiquitination assay, cycloheximide chase, SIRT1 knockdown

    PMID:31043584

    Open questions at the time
    • Acetyltransferase that targets these lysines not identified
    • Interplay between CK2 phosphorylation and SIRT1 deacetylation not studied
  12. 2021 High

    The 'anti-trapper' model was established: XRCC1 prevents toxic PARP1 trapping on BER intermediates, and in its absence PARP1 hyperactivation triggers USP3-mediated histone de-ubiquitination that suppresses transcription — unifying the repair scaffold and transcription-recovery phenotypes under one mechanism.

    Evidence PARP1 chromatin trapping assay, BER intermediate accumulation, PARP1/XRCC1 double KO rescue, EU-incorporation transcription recovery, USP3 KO/inhibition in patient fibroblasts and mouse neurons

    PMID:34102106 PMID:34811483

    Open questions at the time
    • Whether PARP1 trapping contributes to alt-EJ phenotypes not tested
    • Structural basis for how XRCC1 displaces trapped PARP1 unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structural basis for how XRCC1 displaces trapped PARP1 from BER intermediates, the complete spectrum of post-translational modifications governing XRCC1 regulation in vivo, and the extent to which XRCC1's role in alternative end-joining at replication forks contributes to genome instability in BRCA-deficient cancers.
  • No high-resolution structure of full-length XRCC1 in complex with trapped PARP1
  • Complete PTM regulatory network not mapped
  • Alt-EJ role at replication forks studied in single lab only

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 5 GO:0005694 chromosome 3
Pathway
R-HSA-73894 DNA Repair 9 R-HSA-1643685 Disease 1
Partners
APEX1CSNK2A1LIG3PARP1PARP2PCNAPNKPPOLB
Complex memberships
XRCC1–DNA ligase IIIα complexXRCC1–PNK–pol β–ligase III SSBR complexXRCC1–pol β–ligase III–PARP1 BER complex

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Molecular cloning of XRCC1 established it as a 633-amino-acid protein (69.5 kDa) required for efficient DNA single-strand break repair; CHO mutant EM9 cells lacking XRCC1 show reduced strand-break rejoining, elevated sister chromatid exchange, and sensitivity to alkylating agents and ionizing radiation. cDNA cloning, complementation of CHO EM9 mutant, strand-break repair kinetics, cell survival, SCE assays Molecular and cellular biology High 2247054
1994 XRCC1 physically interacts with DNA ligase III in human cells; XRCC1 is required for normal levels of DNA ligase III activity, implicating this ligase in base excision repair. Affinity chromatography (His-tagged XRCC1 co-purification), DNA ligase III activity assay in EM9 cells Molecular and cellular biology High 8264637
1996 XRCC1 directly interacts with DNA polymerase β (pol β) via residues 84–183 in its N-terminal region; the C-terminal region binds DNA ligase III. XRCC1 suppresses strand displacement by pol β during single-nucleotide BER reconstitution, allowing efficient nick ligation. XRCC1 thus functions as a scaffold protein without catalytic activity. BER reconstitution with purified recombinant human proteins, far Western blotting, affinity precipitation, yeast two-hybrid, gel retardation (supershift) assay The EMBO journal High 8978692
1997 Only the 103 kDa isoform of DNA ligase III (not the testis-specific 96 kDa isoform) interacts with XRCC1; the C-terminal 96 amino acids of XRCC1 are necessary and sufficient for the interaction, and the C-terminal 148 amino acids of DNA ligase III contain the XRCC1-binding site. Far Western blotting, affinity precipitation of subcloned XRCC1 and DNA ligase III fragments, antipeptide antibodies Biochemistry High 9136882
1998 XRCC1 physically associates with PARP-1 via its central BRCT I domain (amino acids 301–402); XRCC1 overexpression dramatically decreases PARP-1 activity in vivo, identifying XRCC1 as a negative regulator of PARP-1 and placing PARP-1 in a BER multiprotein complex with XRCC1, pol β, and DNA ligase III. Yeast two-hybrid screen, co-immunoprecipitation in mammalian cells, PARP-1 activity assay after XRCC1 overexpression Molecular and cellular biology High 9584196
2001 XRCC1 interacts with polynucleotide kinase (PNK) and stimulates PNK's DNA kinase and DNA phosphatase activities at damaged DNA termini; XRCC1, pol β, PNK, and DNA ligase III form multiprotein complexes in human cell extracts that together repair oxidative/ionizing-radiation-type single-strand breaks. Co-immunoprecipitation, in vitro DNA kinase/phosphatase activity assays, multi-protein SSB repair assay in cell extracts Cell High 11163244
2001 XRCC1 physically interacts with APE1 and stimulates APE1 endonuclease activity; a truncated APE1 lacking the first 35 amino acids retains catalytic activity but cannot bind XRCC1 and is not stimulated by it. XRCC1-deficient CHO cells have reduced capacity to initiate repair of abasic sites, corrected by XRCC1 expression. Yeast two-hybrid, co-immunoprecipitation, APE1 activity assay with recombinant proteins, AP-site repair assay in XRCC1-deficient cells The EMBO journal High 11707423
2002 PARP-2 interacts with XRCC1 (as well as pol β and DNA ligase III); XRCC1 negatively regulates PARP-2 activity similarly to PARP-1. PARP-2-deficient cells show delayed DNA strand-break resealing after alkylation damage, demonstrating a functional role for PARP-2 in BER alongside XRCC1. Yeast two-hybrid, co-immunoprecipitation, PARP-2 activity assay, PARP-2 knockout mouse cells with strand-break repair kinetics The Journal of biological chemistry High 11948190
2003 PARP-1 is required for assembly/stability of XRCC1 nuclear foci at sites of oxidative DNA damage; XRCC1 foci co-localize with poly(ADP-ribose) synthesis and fail to form in PARP-1-null MEFs or when the XRCC1 BRCT I domain is mutated, demonstrating that PARP-1-generated PAR mediates XRCC1 recruitment. Immunofluorescence microscopy of XRCC1 foci after H2O2, PARP-1 KO MEFs, BRCT I domain point mutants of XRCC1 Nucleic acids research High 14500814
2004 XRCC1 co-localizes with PCNA at DNA replication foci in S phase and physically interacts with PCNA in vivo; in vitro the interaction is mediated by XRCC1 residues 166–310. This suggests XRCC1 is recruited to replication factories via PCNA to facilitate SSBR during S phase. Immunofluorescence co-localization, FRET analysis, co-immunoprecipitation, in vitro binding with XRCC1 fragments Nucleic acids research High 15107487
2004 PARP-1 and the XRCC1–DNA ligase III complex participate in an alternative, DNA-PK-independent pathway for DNA double-strand break end-joining; PARP-1 provides synapsis activity and XRCC1–ligase III provides ligation in this alt-EJ route. In vitro synapsis and end-joining two-step assay with nuclear extracts and recombinant proteins, PARP inhibitor cytotoxicity, DSB repair kinetics The Journal of biological chemistry High 15498778
2005 The primary biochemical defect in XRCC1-deficient cells is impaired nick ligation (~2–4-fold reduction); base excision (8-oxoG, 5-HC, εA, uracil), AP-site incision, and pol β gap-filling activities are normal in XRCC1-deficient extracts, demonstrating XRCC1's key role is at the ligation step of BER/SSBR. Whole-cell extract BER and SSBR assays, 8-oxoG and AP-site measurement by HPLC/GC-MS in EM9 cells Biochemistry High 16245950
2010 Casein kinase 2 (CK2) is the major kinase phosphorylating XRCC1 in human cell extracts; CK2-mediated phosphorylation stabilizes the XRCC1–DNA ligase IIIα complex, and mutation of CK2 phosphorylation sites or CK2 siRNA knockdown destabilizes the complex, reduces ligase III levels, and causes accumulation of DNA strand breaks. Unbiased kinase activity assay in cell extracts, CK2 siRNA knockdown, CK2-site mutants of XRCC1, co-immunoprecipitation, comet assay DNA repair High 20471329
2011 Conditional neural knockout studies reveal that DNA ligase 1 (not ligase III) is the main ligase for XRCC1-mediated nuclear DNA repair; LIG3's essential function is in mitochondrial DNA maintenance, dissociating the cellular roles of XRCC1 and LIG3. Tissue-specific (neural) conditional knockout mice for XRCC1 and LIG3, phenotypic comparison, mitochondrial DNA maintenance assays Cell cycle (Georgetown, Tex.) High 21636980
2015 The phosphate-binding pocket of the XRCC1 BRCT1 domain selectively binds poly(ADP-ribose) at low PAR levels and is required for interaction with cellular PARP-1, XRCC1 accumulation at UVA/H2O2 damage sites and PCNA foci, and XRCC1-dependent acceleration of SSBR, BER, and cell survival after DNA damage. PAR-binding assays with BRCT1 mutants, co-immunoprecipitation with PARP-1, EGFP-XRCC1 live-cell damage-recruitment assays, BER/SSBR reporter assays, clonogenic survival Nucleic acids research High 26130715
2016 Biallelic loss-of-function mutations in human XRCC1 cause ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia, associated with reduced SSBR and elevated protein ADP-ribosylation (PARP hyperactivation). Genetic deletion of Parp1 in Xrcc1-deficient mice rescues cerebellar ADP-ribose levels, reduces cerebellar neuron loss, and alleviates ataxia, identifying PARP1 hyperactivation as the pathogenic mechanism. Patient cell studies (SSBR rates, PAR levels), Xrcc1/Parp1 double-KO mouse model, cerebellar neuron counting, ADP-ribosylation quantification Nature High 28002403
2016 XRCC1 is an indispensable mediator of muscle differentiation: caspase-triggered DNA strand breaks during myoblast differentiation are rapidly followed by XRCC1 repair foci formation in myonuclei, and skeletal-myoblast-specific deletion of Xrcc1 does not affect cell growth but causes perinatal lethality with sustained DNA damage and impaired myofiber development. Conditional Xrcc1 knockout in skeletal myoblasts, immunofluorescence of XRCC1 repair foci, γH2AX staining, myofiber morphology analysis Cell discovery High 27462438
2017 Either PARP1 or PARP2 alone is sufficient for near-normal XRCC1 recruitment to oxidative single-strand breaks; loss of both PARP1 and PARP2 together is required to greatly reduce or ablate XRCC1 chromatin binding after H2O2. Very low levels of ADP-ribosylation (by either enzyme) are sufficient for XRCC1 recruitment. PNKP recruitment similarly requires PARP1/2 redundancy. Isogenic PARP1/PARP2/PARP3 single and double KO human diploid cells, H2O2-induced XRCC1 and PNKP chromatin fractionation, PARP inhibitor dose-response Nucleic acids research High 27965414
2018 KDM5B demethylates H3K4 at DNA damage sites and facilitates XRCC1 recruitment; increased KDM5B in cisplatin-resistant gastric cancer cells promotes H3K4 demethylation, enabling XRCC1 co-localization with γH2AX. HSP90 stabilizes KDM5B via direct complex formation. KDM5B or HSP90 inhibition blocks XRCC1 recruitment to damage, restoring drug sensitivity. Co-immunoprecipitation, γH2AX/XRCC1 co-localization imaging, KDM5B knockdown/overexpression, JIB-04 inhibitor, HSP90 inhibitor 17-AAG, mass spectrometry International journal of biological sciences Medium 29989047
2018 PNKP interacts with XRCC1 through two distinct interfaces: the PNKP FHA domain binds phosphorylated XRCC1 (extending beyond residues 515–526), and an XRCC1 fragment (residues 166–436) binds the PNKP catalytic domain and tightly activates PNKP kinase activity. XRCC1 SNP variants R194W and R280H show substantially weaker PNKP binding and severely reduced PNKP stimulation, and cells expressing these variants show reduced PNKP recruitment to laser-induced DNA damage. In vitro binding and PNKP kinase activity assays with recombinant XRCC1 fragments and SNP variants, laser microirradiation/live-cell recruitment imaging The Journal of biological chemistry High 30446622
2019 SIRT1 deacetylates XRCC1 at lysines K260, K298, and K431, preventing β-TrCP-mediated ubiquitination and proteasomal degradation of XRCC1. Mutations at these three sites abrogate β-TrCP interaction and prolong XRCC1 half-life; SIRT1 knockdown reduces XRCC1 stability and enhances DNA damage, contributing to chemoresistance. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis, cycloheximide chase (half-life), SIRT1 KD by siRNA/inhibitor Cell death & disease High 31043584
2019 XRCC1 contains a central DNA-binding domain (CDB, residues 219–415) encompassing the BRCT1 domain that lacks specificity for nicked/gapped DNA. Alanine substitution of CDB residues abolishes DNA binding in vitro and significantly reduces XRCC1 retention (but not initial recruitment) at DNA damage sites, and reduced retention is associated with an increased rate of repair, suggesting DNA binding regulates dwell time at damage. Electrophoretic mobility shift assay, alanine scanning mutagenesis, live-cell XRCC1-GFP retention assay at laser-induced damage sites Scientific reports High 30816207
2020 After replication stress, XRCC1 forms an active repair complex with POLQ and MRE11 that supports alternative end-joining (alt-EJ) in vitro; BRCA2 normally limits XRCC1 recruitment to suppress alt-EJ at stalled forks. Without BRCA2 fork protection, XRCC1 enables replication completion via MRE11-dependent fork resection and restart, at the cost of increased genome instability. In vitro alt-EJ reconstitution with XRCC1/POLQ/MRE11, BRCA2-XRCC1 co-depletion, fork restart/resection assays, chromosome aberration analysis NAR cancer Medium 32776008
2021 XRCC1 prevents 'toxic PARP1 trapping' during BER: protein complexes of pol β and DNA ligase III assembled by XRCC1 prevent excessive PARP1 engagement at BER intermediates. In XRCC1-deficient cells (and patient fibroblasts), PARP1 becomes trapped on BER intermediates—similar to PARP-inhibitor trapping—blocking pol β access and impeding repair. PARP1 deletion rescues BER and resistance to base damage in XRCC1−/− cells. Trapping assay (PARP1 chromatin fractionation), BER intermediate accumulation assay, PARP1-XRCC1 double KO cells, patient-derived fibroblasts, base damage sensitivity (clonogenic) Molecular cell High 34102106
2021 XRCC1-deficient human cells and patient fibroblasts fail to recover transcription after DNA base damage due to excessive/aberrant PARP1 activity during BER. This aberrant PARP1 activity promotes excessive recruitment of ubiquitin protease USP3, which reduces monoubiquitinated histones required for normal transcription. Inhibition or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1−/− cells. Transcription recovery assay (EU incorporation) in XRCC1 KO cells, patient fibroblasts, Xrcc1−/− neurons; PARP1 and USP3 KO/inhibition rescue experiments; ubiquitin-histone western blotting Nature cell biology High 34811483
2022 XRCC1 and PARP1 exhibit a reciprocal relationship at DNA damage sites: recruitment of each protein is impeded in the absence of the other. XRCC1 KO cells show hypersensitivity (excess NAD+ depletion, cytotoxicity) to topoisomerase I inhibitor camptothecin compared to PARP1 KO cells, and additional PARP1 deletion or pharmacological PARP inhibition rescues this hypersensitivity and partially restores DNA repair in XRCC1 KO cells. PARP1 KO, XRCC1 KO, and PARP1/XRCC1 double KO HeLa cells; PARylation assay, NAD+ quantification, clonogenic survival, cell-cycle analysis, comet assay Cell biology and toxicology High 35778544

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1994 The 1993-94 Généthon human genetic linkage map. Nature genetics 2146 7545953
2013 Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells. Science (New York, N.Y.) 1480 24292625
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2005 Nucleolar proteome dynamics. Nature 934 15635413
1998 XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Molecular and cellular biology 786 9584196
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
1996 Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase beta and the XRCC1 protein. The EMBO journal 644 8978692
1998 Nonconservative amino acid substitution variants exist at polymorphic frequency in DNA repair genes in healthy humans. Cancer research 640 9485007
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2002 Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision DNA repair in association with PARP-1 and XRCC1. The Journal of biological chemistry 574 11948190
2004 Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. The Journal of biological chemistry 556 15498778
2003 A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic acids research 548 14500814
2001 XRCC1 stimulates human polynucleotide kinase activity at damaged DNA termini and accelerates DNA single-strand break repair. Cell 506 11163244
2009 Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science (New York, N.Y.) 496 19661379
1994 An interaction between the mammalian DNA repair protein XRCC1 and DNA ligase III. Molecular and cellular biology 437 8264637
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. American journal of epidemiology 431 16221808
2001 XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 404 11532866
2004 AP endonuclease-independent DNA base excision repair in human cells. Molecular cell 403 15260972
2001 XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions. The EMBO journal 392 11707423
2000 Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells. Carcinogenesis 392 10783319
1990 Molecular cloning of the human XRCC1 gene, which corrects defective DNA strand break repair and sister chromatid exchange. Molecular and cellular biology 368 2247054
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1997 XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry 226 9136882
2016 XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature 219 28002403
2011 Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials. BJU international 212 21952069
2019 The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of advanced renal cell carcinoma (RCC). Journal for immunotherapy of cancer 199 31856918
2010 Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. The American journal of surgical pathology 173 20679884
2017 Overlapping roles for PARP1 and PARP2 in the recruitment of endogenous XRCC1 and PNKP into oxidized chromatin. Nucleic acids research 163 27965414
2004 XRCC1 co-localizes and physically interacts with PCNA. Nucleic acids research 162 15107487
2003 Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer letters 158 12565173
2021 XRCC1 prevents toxic PARP1 trapping during DNA base excision repair. Molecular cell 155 34102106
2017 LncRNA-SARCC suppresses renal cell carcinoma (RCC) progression via altering the androgen receptor(AR)/miRNA-143-3p signals. Cell death and differentiation 136 28644440
2019 XRCC1 protein; Form and function. DNA repair 134 31324530
2000 Molecular cloning, functional expression and characterisation of RCC reductase involved in chlorophyll catabolism. The Plant journal : for cell and molecular biology 116 10743659
2015 The structural basis of XRCC1-mediated DNA repair. DNA repair 108 25795425
2002 XRCC1 polymorphisms and head and neck cancer. Cancer letters 94 11867203
2015 The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function. Nucleic acids research 93 26130715
2002 Genetic polymorphisms of XRCC1 and risk of gastric cancer. Cancer letters 87 12359351
2006 Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma. Carcinogenesis 70 16621887
2006 Polymorphisms in XRCC1, XRCC3, and CCND1 and survival after treatment for metastatic breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 67 17116943
2006 Mouse models of XRCC1 DNA repair polymorphisms and cancer. Oncogene 62 16550161
2010 Genetic variants of XRCC1, APE1, and ADPRT genes and risk of bladder cancer. DNA and cell biology 58 20218899
2021 XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair. Nature cell biology 55 34811483
2018 KDM5B demethylates H3K4 to recruit XRCC1 and promote chemoresistance. International journal of biological sciences 55 29989047
2019 A Review of Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) in Renal Cell Carcinoma (RCC). Molecular imaging and biology 53 30617728
2014 Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). BJU international 53 24053727
2012 Clinicopathological and functional significance of XRCC1 expression in ovarian cancer. International journal of cancer 53 23225521
2004 Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer. Cancer letters 52 15533591
2022 STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 51 36445063
2019 SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer. Cell death & disease 51 31043584
2005 Polymorphisms of XRCC1 gene, alcohol consumption and colorectal cancer. International journal of cancer 51 15800946
2011 Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis. Molecular biology reports 50 21604176
2010 XRCC1 phosphorylation by CK2 is required for its stability and efficient DNA repair. DNA repair 50 20471329
2007 XRCC1 and XPD polymorphisms and esophageal adenocarcinoma risk. Carcinogenesis 50 17264068
2020 XRCC1 promotes replication restart, nascent fork degradation and mutagenic DNA repair in BRCA2-deficient cells. NAR cancer 46 32776008
2015 A river model to map convergent cancer evolution and guide therapy in RCC. Nature reviews. Urology 46 26526752
2021 Androgen receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM) via altering TWIST1 nonsense-mediated decay through lncRNA-TANAR. Oncogene 45 33510354
2018 Renal Cell Carcinoma (RCC) Tumors Display Large Expansion of Double Positive (DP) CD4+CD8+ T Cells With Expression of Exhaustion Markers. Frontiers in immunology 45 30534127
2020 XRCC1 - Strategies for coordinating and assembling a versatile DNA damage response. DNA repair 42 33087283
2012 Epigenetic regulation in RCC: opportunities for therapeutic intervention? Nature reviews. Urology 42 22249190
2003 CYP1A1 and XRCC1 gene polymorphisms in SCC of the larynx. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 42 14639127
2014 The impact of perioperative blood transfusion on survival after nephrectomy for non-metastatic renal cell carcinoma (RCC). BJU international 40 24471825
2007 Menopausal age and XRCC1 gene polymorphisms: role in breast cancer risk. Cancer detection and prevention 39 17935911
2011 The complex roles of Wnt antagonists in RCC. Nature reviews. Urology 38 22025172
2015 Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status. Oncotarget 37 26304926
2009 Polymorphisms of XRCC1 gene and risk of gastric cardiac adenocarcinoma. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 37 19673050
2015 Infiltrating neutrophils promote renal cell carcinoma (RCC) proliferation via modulating androgen receptor (AR) → c-Myc signals. Cancer letters 36 26231735
2009 Cytoreductive nephrectomy for metastatic RCC in the era of targeted therapy. Nature reviews. Urology 36 19528960
2021 Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC. Journal for immunotherapy of cancer 35 33658305
2019 SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3. Experimental cell research 34 31201813
2016 Loss of DAB2IP in RCC cells enhances their growth and resistance to mTOR-targeted therapies. Oncogene 34 26876207
2019 Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities. Nature reviews. Urology 32 31602010
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2016 SUSD2 is frequently downregulated and functions as a tumor suppressor in RCC and lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 31 26815503
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2016 Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 26938431
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2012 MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer. Genetics and molecular research : GMR 23 22843073
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2008 Characterization of plant XRCC1 and its interaction with proliferating cell nuclear antigen. Planta 22 18247046
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