Affinage

XRCC1

DNA repair protein XRCC1 · UniProt P18887

Length
633 aa
Mass
69.5 kDa
Annotated
2026-06-11
100 papers in source corpus 23 papers cited in narrative 23 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

XRCC1 is a non-enzymatic scaffold protein that coordinates DNA single-strand break repair (SSBR) and base excision repair (BER) by physically organizing and stimulating the enzymatic machinery at break sites (PMID:9136882, PMID:16245950). It selectively recognizes short-gap single-strand breaks through dedicated DNA-binding activity, with an N-terminal preference for gaps ≤1 nucleotide and a central BRCT1-containing DNA-binding domain (residues 219–415) that mediates retention rather than initial recruitment (PMID:15610045, PMID:30816207). XRCC1 is recruited to damage via its BRCT1 phosphate-binding pocket, which binds PARP1-synthesized poly(ADP-ribose) and is required for accumulation at laser-, H2O2-, and replication-associated damage (PMID:26130715). Once positioned, XRCC1 directly partners with the 103 kDa form of DNA ligase IIIα, DNA polymerase β, and polynucleotide kinase phosphatase (PNKP), stimulating PNKP catalysis by enhancing terminus discrimination and accelerating enzyme turnover (PMID:9136882, PMID:17650498, PMID:30446622); the principal biochemical consequence of XRCC1 loss is a defect at the ligation step of BER/SSBR (PMID:16245950). Complex architecture and stability are tuned post-translationally: CK2 phosphorylation maintains the XRCC1–ligase IIIα complex and licenses PNKP recruitment, DNA-PK phosphorylation at S371 dissociates XRCC1 dimers and supports DSB repair, and heterodimer formation plus HSP90 binding protect XRCC1 and Polβ from CHIP-mediated degradation (PMID:16397295, PMID:20471329, PMID:25423885, PMID:29100039). Beyond catalyzing repair, XRCC1 acts as an anti-trapper that restrains excessive PARP1 engagement on BER intermediates; in its absence PARP1 becomes trapped and hyperactivated, blocking repair-enzyme access, suppressing transcriptional recovery through USP3-driven loss of histone monoubiquitination, and driving cerebellar neurodegeneration that is rescued by PARP1 deletion (PMID:34102106, PMID:34811483, PMID:28002403, PMID:35778544). Biallelic XRCC1 mutations cause a human SSBR-deficiency syndrome with PARP1 hyperactivation and cerebellar ataxia (PMID:28002403).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1992 Medium

    Established that XRCC1 is expressed at elevated levels in specific tissues, raising the question of where its repair function is most critical.

    Evidence Northern and Western analysis across rat tissues

    PMID:1353960

    Open questions at the time
    • Expression pattern alone does not define molecular function
    • Functional role in meiosis/recombination inferred, not tested
  2. 1997 High

    Identified the first direct partner of XRCC1, defining it as a scaffold that recruits a ligase rather than acting catalytically itself.

    Evidence Far Western and affinity precipitation with XRCC1 and DNA ligase III truncation fragments, isoform-specific antibodies

    PMID:9136882

    Open questions at the time
    • Did not establish which ligase performs nuclear repair in vivo
    • Functional consequence of the interaction not measured
  3. 2004 High

    Showed XRCC1 selectively recognizes short-gap single-strand breaks and is recruited to replication factories via PCNA, linking scaffold function to substrate specificity and S-phase repair.

    Evidence Sedimentation equilibrium and fluorescence titration with defined DNA substrates; FRET, Co-IP, and in vitro domain mapping in HeLa cells

    PMID:15107487 PMID:15610045

    Open questions at the time
    • Structural basis of gap-length discrimination not resolved
    • Physiological contribution of the PCNA interaction to repair not quantified
  4. 2006 High

    Defined DNA-PK phosphorylation of XRCC1 at S371 as a regulatory switch controlling dimer state and DSB repair, extending XRCC1 function beyond SSBR.

    Evidence BRCT1 pulldown-MS, in vitro kinase assays, S371 mutant rescue of EM9 cells

    PMID:16397295

    Open questions at the time
    • Mechanistic link between dimer dissociation and DSB repair unresolved
    • Direct DSB substrate engagement not shown
  5. 2007 High

    Demonstrated XRCC1 mechanistically stimulates PNK by enhancing terminus discrimination and accelerating turnover, showing scaffold activity directly tunes enzyme kinetics.

    Evidence Reconstituted fluorescence binding, anisotropy, and kinetic assays with PNK on defined substrates

    PMID:17650498

    Open questions at the time
    • Domain of XRCC1 mediating stimulation not mapped here
    • In vivo relevance of turnover acceleration not tested
  6. 2005 High

    Pinpointed the ligation step as the primary biochemical defect in XRCC1 deficiency, narrowing its essential function within the BER pathway.

    Evidence Stepwise BER reconstitution assays in EM9 versus wild-type CHO extracts

    PMID:16245950

    Open questions at the time
    • Did not identify the responsible ligase in vivo
    • Whole-extract assay may mask redundant activities
  7. 2008 High

    Identified E2F1 as a direct transcriptional activator of XRCC1, connecting repair capacity to cell-cycle and damage-responsive gene regulation.

    Evidence Promoter luciferase reporters, E2F1 binding-site mutagenesis, E2F1-/- MEF repair assays

    PMID:18348985

    Open questions at the time
    • Other transcriptional inputs not surveyed
    • Quantitative contribution to damage-induced repair not isolated
  8. 2010 High

    Established CK2 as the dominant XRCC1 kinase required for complex stability, linking phosphorylation to ligase IIIα levels and genome integrity.

    Evidence Unbiased kinase assay, CK2-site mutagenesis, CK2 siRNA with comet assay

    PMID:20471329

    Open questions at the time
    • Did not resolve which phosphosites drive which downstream events
    • Direct structural effect on complex not shown
  9. 2011 High

    Resolved the in vivo ligase question by showing Ligase I, not Ligase III, performs XRCC1-mediated nuclear repair, with LIG3 dedicated to mitochondrial DNA.

    Evidence Nervous-system-specific conditional XRCC1 and LIG3 knockout mice with mitochondrial DNA analysis

    PMID:21636980

    Open questions at the time
    • Mechanism of ligase choice not defined
    • Tissue specificity of ligase usage outside nervous system not addressed
  10. 2014 High

    Reframed the Polβ and HSP90 interactions as stability/quality-control functions rather than recruitment, revealing proteostatic regulation of repair-complex architecture.

    Evidence Co-IP, ubiquitylation assays, HSP90 inhibition, siRNA, and live-cell imaging

    PMID:25423885

    Open questions at the time
    • How proliferation/damage signals remodel the complex not fully defined
    • CHIP recognition determinants not mapped
  11. 2015 High

    Identified the BRCT1 phosphate-binding pocket as the PAR-reading module that recruits XRCC1 to damage, defining the mechanism of PARP1-dependent recruitment.

    Evidence Pocket mutagenesis, PAR binding assays, live-cell laser recruitment, PARP1 Co-IP, survival assays

    PMID:26130715

    Open questions at the time
    • Structural detail of PAR-pocket binding not resolved
    • Relative contribution versus direct DNA binding not quantified
  12. 2016 High

    Established that XRCC1 loss causes PARP1 hyperactivation as the mechanistic driver of cerebellar neurodegeneration, providing a disease mechanism and therapeutic rationale.

    Evidence Patient fibroblasts and Xrcc1/Parp1 double-knockout mice with ADP-ribose, neuron counting, and ataxia readouts

    PMID:28002403

    Open questions at the time
    • Molecular trigger of PARP1 hyperactivation not yet defined at this stage
    • Why cerebellum is selectively vulnerable unresolved
  13. 2016 High

    Revealed a temporally required XRCC1 repair function in terminal muscle differentiation, extending its role to developmental contexts.

    Evidence Skeletal myoblast-specific Xrcc1 deletion, live foci imaging, perinatal lethality and myofiber histology

    PMID:27462438

    Open questions at the time
    • Source of caspase-triggered DNA breaks in differentiation not defined
    • Whether the defect is BER-specific not established
  14. 2017 High

    Showed CK2-dependent phosphorylation licenses PNKP recruitment but is dispensable for some XRCC1 repair, dissociating PNKP-dependent and -independent functions.

    Evidence Phosphorylation-mutant complementation in Xrcc1-/- fibroblasts, PNKP-GFP recruitment imaging, CPT/H2O2 survival

    PMID:29100039

    Open questions at the time
    • Identity of the PNKP-independent repair route not defined
    • Why CPT hypersensitivity reverses with the mutant unclear
  15. 2018 High

    Mapped a PNKP/DNA-binding region and showed cancer-associated R194W and R280H variants impair PNKP stimulation and recruitment, giving functional meaning to common polymorphisms.

    Evidence Domain binding and PNKP kinase assays with XRCC1 fragments; laser recruitment imaging of variants

    PMID:30446622

    Open questions at the time
    • Cancer risk consequences in patients not tested here
    • Structural basis of variant defects not resolved
  16. 2018 Medium

    Connected chromatin state to XRCC1 recruitment by showing KDM5B-mediated H3K4 demethylation facilitates XRCC1 localization to damage and contributes to cisplatin resistance.

    Evidence KDM5B manipulation, Co-IP, XRCC1/γH2AX co-localization, H3K4 methylation and pharmacological inhibition

    PMID:29989047

    Open questions at the time
    • Link between demethylation and recruitment inferred from co-localization, not biochemically reconstituted
    • Direct XRCC1–chromatin contact not demonstrated
  17. 2019 High

    Defined post-translational control of XRCC1 abundance, with SIRT1 deacetylation blocking β-TrCP ubiquitination and a central DNA-binding domain governing retention versus repair rate.

    Evidence Co-IP, deacetylation-site mutagenesis, ubiquitination and half-life assays; CDB mutagenesis with in vitro binding and live-cell retention imaging

    PMID:30816207 PMID:31043584

    Open questions at the time
    • How retention duration is normally set in vivo unclear
    • Coupling of acetylation status to repair activity not established
  18. 2020 Medium

    Uncovered a non-canonical XRCC1 role in alternative end-joining at stalled forks via a POLQ/MRE11 complex normally restrained by BRCA2, linking XRCC1 to replication-stress tolerance.

    Evidence In vitro alt-EJ reconstitution, Co-IP with POLQ/MRE11, BRCA2/XRCC1 co-depletion, fork restart and aberration assays

    PMID:32776008

    Open questions at the time
    • Single-lab reconstitution in a novel pathway context
    • In vivo significance of XRCC1-driven alt-EJ not established
  19. 2021 High

    Defined XRCC1 as an anti-trapper that prevents PARP1 from becoming trapped on BER intermediates and showed aberrant PARP1 activity blocks transcriptional recovery via USP3, unifying the toxicity mechanism of XRCC1 loss.

    Evidence XRCC1-knockout cells, PARP1 trapping and BER accessibility assays, PARP1/USP3 deletion epistasis, histone ubiquitination and transcription recovery in neurons and patient fibroblasts

    PMID:34102106 PMID:34811483

    Open questions at the time
    • Structural basis of how XRCC1 displaces/limits PARP1 unresolved
    • Generality of transcription-block mechanism across tissues not fully tested
  20. 2022 High

    Established a reciprocal recruitment dependency between PARP1 and XRCC1 and confirmed that PARP1 deletion partially rescues XRCC1-deficient repair and survival.

    Evidence PARP1/XRCC1 single and double KO HeLa cells, live recruitment imaging, NAD+, survival, and comet assays

    PMID:35778544

    Open questions at the time
    • Mechanism of the mutual recruitment dependency not resolved
    • Only partial rescue indicates additional PARP1-independent defects

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural mechanism by which XRCC1 physically limits and displaces PARP1 on BER intermediates, and how its multiple recruitment cues (PAR, direct DNA, chromatin marks) are integrated, remain undefined.
  • No high-resolution structure of an XRCC1-bound repair intermediate with PARP1
  • Quantitative hierarchy among PAR-, DNA-, and chromatin-based recruitment unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0003677 DNA binding 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-1643685 Disease 1
Partners
HSP90LIG3MRE11PARP1PCNAPNKPPOLBPOLQ
Complex memberships
XRCC1–DNA ligase IIIα complexXRCC1–POLQ–MRE11 alt-EJ complexXRCC1–Polβ heterodimer

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 The C-terminal 96 amino acids of XRCC1 are necessary and sufficient for direct interaction with DNA ligase III (103 kDa form), and the C-terminal 148 amino acids of DNA ligase III contain the binding site for XRCC1. The alternatively spliced 96 kDa testis form of DNA ligase III lacks this interaction, indicating only the 103 kDa isoform partners with XRCC1 in base excision repair. Far Western analysis and affinity precipitation with subcloned XRCC1 and DNA ligase III fragments; antipeptide antibodies to distinguish isoforms Biochemistry High 9136882
2004 XRCC1 co-localizes with PCNA at DNA replication foci exclusively in S phase of undamaged HeLa cells, physically interacts with PCNA in vivo (shown by FRET and co-immunoprecipitation), and the interaction is mediated by XRCC1 residues 166–310 in vitro, suggesting XRCC1 is sequestered to replication factories via PCNA to facilitate single-strand break repair in S phase. Fluorescence co-localization, FRET analysis, co-immunoprecipitation, in vitro biochemical assay with XRCC1 truncation fragments Nucleic acids research High 15107487
2006 XRCC1 is phosphorylated at serine 371 by the DNA-PK complex (interacting via the BRCT1 domain) in response to ionizing radiation. This phosphorylation causes XRCC1 dimer dissociation. The non-phosphorylable S371L mutant fails to fully rescue DSB repair defects in XRCC1-deficient EM9 cells, establishing a functional role for DNA-PK-mediated XRCC1 phosphorylation in DSB repair. XRCC1 also strongly stimulates DNA-PK-mediated phosphorylation of p53-Ser15. GST-BRCT1 pulldown followed by mass spectrometry; phosphorylation assays; XRCC1 mutant (S371D and S371L) rescue of EM9 cells; in vitro kinase assay Nucleic acids research High 16397295
2007 XRCC1 stimulates polynucleotide kinase (PNK) activity by two mechanisms: (1) enhancing PNK's ability to discriminate between 5'-OH and 5'-phosphate termini at strand breaks, and (2) displacing PNK from the phosphorylated DNA product, thereby accelerating PNK turnover. Fluorescence binding assays, fluorescence anisotropy, kinetic assays at limiting enzyme concentration with XRCC1 and PNK on defined DNA substrates The Journal of biological chemistry High 17650498
2010 Casein kinase 2 (CK2) is the major kinase responsible for XRCC1 phosphorylation in human cell extracts. CK2-mediated phosphorylation is required for stability of the XRCC1–DNA ligase IIIα complex; mutation of CK2 phosphorylation sites in XRCC1 destabilizes this complex. siRNA knockdown of CK2 reduces XRCC1 phosphorylation and stability, decreases Lig III levels, and leads to accumulation of DNA strand breaks. Unbiased kinase activity assay in cell extracts; site-directed mutagenesis of CK2 phosphorylation sites; siRNA knockdown of CK2; comet assay for strand breaks DNA repair High 20471329
2004 Purified full-length human XRCC1 exists as a monomer at low concentrations and forms a dimer at higher concentrations (Kd ~570 nM). It preferentially binds DNA containing single-strand breaks with gaps ≤1 nucleotide (Kd 34–65 nM) compared to 5-nucleotide gaps, intact duplex, or single-stranded DNA (Kd ~215–260 nM), indicating selective recognition of short-gap SSBs. Sedimentation equilibrium ultracentrifugation, fluorescence titration binding assays with defined model DNA substrates Biochemistry High 15610045
2015 The phosphate-binding pocket within XRCC1's central BRCT1 domain is required for selective binding to poly(ADP-ribose) (PAR) at low ADP-ribosylation levels and promotes interaction with cellular PARP1. This pocket is required for XRCC1 recruitment to UVA laser, H2O2 damage sites, and sub-nuclear PCNA foci, and is essential for XRCC1-dependent acceleration of SSBR, BER, and cell survival after DNA damage. Mutagenesis of phosphate-binding pocket residues; PAR binding assays; EGFP-XRCC1 live-cell recruitment at laser-induced damage; co-immunoprecipitation with PARP1; clonogenic survival and repair kinetics assays Nucleic acids research High 26130715
2014 The XRCC1–DNA polymerase β heterodimer is not required for DNA damage response or recruitment to damage sites; instead, heterodimer formation protects Polβ from CHIP-mediated ubiquitylation and degradation. XRCC1 monomer stability is independently protected from CHIP by binding to HSP90. In response to cellular proliferation and DNA damage, HSP90- and proteasome-mediated regulation alters the repair complex architecture. Co-immunoprecipitation; ubiquitylation assays; HSP90 inhibitor (17-AAG) treatment; siRNA knockdown; live-cell imaging of DNA damage response Nature communications High 25423885
2016 Biallelic XRCC1 mutations in patients cause elevated PARP1 hyperactivation (elevated protein ADP-ribosylation) and single-strand break repair deficiency. Genetic deletion of Parp1 in Xrcc1-deficient mice rescues normal cerebellar ADP-ribose levels, reduces cerebellar neuron loss, and reduces ataxia, establishing that PARP1 hyperactivation caused by loss of XRCC1 is the mechanistic driver of cerebellar neuropathology. Patient-derived fibroblast analysis; Xrcc1/Parp1 double-knockout mouse model; ADP-ribosylation quantification; cerebellar neuron counting; behavioral ataxia scoring Nature High 28002403
2021 XRCC1 assembles complexes containing DNA polymerase β and DNA ligase III that prevent excessive PARP1 engagement and activity during BER. In XRCC1-deficient cells, PARP1 becomes 'trapped' on BER intermediates (similar to PARP inhibitor trapping), blocking access of repair enzymes such as Polβ. Deletion of PARP1 rescues BER and resistance to base damage in XRCC1-knockout cells. XRCC1-knockout cell lines; PARP1 trapping assays; BER intermediate accessibility assays; PARP1 deletion epistasis; patient fibroblast validation Molecular cell High 34102106
2021 XRCC1 loss causes failure to recover transcription after DNA base damage due to aberrant/excessive PARP1 activity during BER. This aberrant PARP1 activity promotes excessive recruitment of the ubiquitin protease USP3, which reduces monoubiquitinated histones required for normal transcriptional regulation. Inhibition or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1-deficient cells. XRCC1-knockout human cells and Xrcc1-/- mouse neurons; transcription recovery assays; USP3 inhibition/deletion; histone ubiquitination measurement; PARP1 inhibition rescue Nature cell biology High 34811483
2005 XRCC1-deficient cell extracts have normal base excision activity for 8-oxoguanine, 5-hydroxycytosine, ethenoadenine, and uracil; normal abasic site incision; and normal gap-filling. However, a ~2–4-fold reduction in nick ligation activity is observed, indicating that the primary biochemical defect of XRCC1 deficiency is at the ligation step of BER/SSBR. Whole-cell extract BER assays; DNA damage measurement (8-OH-dG levels); nick ligation assays with defined substrates in XRCC1-deficient (EM9) versus wild-type CHO extracts Biochemistry High 16245950
2008 E2F1 transcription factor directly activates XRCC1 promoter transcription via E2F1 binding sites in the promoter. Ectopic wild-type E2F1 (but not a DNA-binding mutant) increases endogenous XRCC1 expression. DNA damage stimulates XRCC1 expression in E2F1+/+ but not E2F1-/- MEFs, and E2F1-/- MEFs show attenuated DNA repair after MMS treatment. Luciferase reporter assays with XRCC1 promoter deletions; conditional E2F1 expression; E2F1-/- MEF analysis; promoter E2F1 binding site deletion mutagenesis; MMS survival and repair assays The Journal of biological chemistry High 18348985
2011 Genetic inactivation of LIG3 (DNA Ligase III) specifically in the nervous system reveals that LIG3 function is central to mitochondrial DNA maintenance rather than nuclear SSBR, in contrast to XRCC1. The data indicate that DNA Ligase 1 (not LIG3) is the main DNA ligase for XRCC1-mediated nuclear DNA repair. Conditional tissue-specific knockout mouse models for XRCC1 and LIG3 in developing nervous system; phenotypic comparison; mitochondrial DNA integrity analysis Cell cycle (Georgetown, Tex.) High 21636980
2016 XRCC1 is an indispensable mediator of muscle differentiation. Caspase-triggered XRCC1 repair foci form rapidly within differentiating myonuclei and then dissipate. Skeletal myoblast-specific deletion of Xrcc1 does not affect cell growth but causes perinatal lethality with sustained DNA damage and impaired myofiber development, demonstrating a temporally required DNA repair function for terminal differentiation. Conditional Xrcc1 deletion in skeletal myoblasts; live-cell XRCC1 repair foci imaging; perinatal lethality and myofiber histology; DNA damage markers Cell discovery High 27462438
2019 SIRT1 binds and deacetylates XRCC1 at lysine residues K260, K298, and K431, preventing β-TrCP E3 ligase-mediated poly-ubiquitination and proteasomal degradation of XRCC1. Mutations of these three lysine sites abrogate interaction with β-TrCP and prolong XRCC1 protein half-life, conferring chemoresistance. Co-immunoprecipitation; SIRT1 knockdown/inhibition; ubiquitination assays; site-directed mutagenesis of XRCC1 lysine residues; cycloheximide chase for protein half-life Cell death & disease High 31043584
2018 KDM5B demethylase demethylates H3K4 at DNA damage sites and facilitates recruitment of XRCC1 to γH2AX-marked damage. KDM5B knockdown increases H3K4 methylation and blocks XRCC1 localization to DNA damage sites. HSP90 protects KDM5B from ubiquitin-dependent proteasomal degradation, and the HSP90–KDM5B–XRCC1 axis mediates cisplatin resistance. KDM5B knockdown/overexpression; co-immunoprecipitation (HSP90–KDM5B); co-localization of XRCC1 with γH2AX; H3K4 methylation analysis; JIB-04 and 17-AAG pharmacological inhibition; mass spectrometry International journal of biological sciences Medium 29989047
2019 XRCC1 contains a central DNA binding domain (CDB, residues 219–415) encompassing the BRCT1 domain. Unlike the N-terminal domain, the CDB binds DNA without specificity for nicked or gapped substrates. Alanine substitutions in the CDB disrupt DNA binding in vitro and reduce XRCC1 retention (but not initial recruitment) at DNA damage sites, and reduced retention is associated with an increased rate of repair. XRCC1 domain truncation/mutagenesis; in vitro DNA binding assays; laser microirradiation with live-cell fluorescence imaging of XRCC1 accumulation kinetics Scientific reports High 30816207
2018 XRCC1 residues 166–436 bind tightly to PNKP and DNA and efficiently activate PNKP's kinase activity. Cancer-associated SNP variants R194W and R280H in this fragment show considerably weaker PNKP interaction and severely reduced stimulation of PNKP kinase activity. In cells, these XRCC1 variants show reduced ability to recruit PNKP to laser-microirradiation-induced DNA damage sites. Domain binding assays; PNKP kinase activity assays with XRCC1 fragments; laser microirradiation with fluorescence microscopy of PNKP recruitment The Journal of biological chemistry High 30446622
2017 CK2-mediated phosphorylation of XRCC1 at multiple consensus sites is required for PNKP binding to XRCC1 and efficient PNKP recruitment to DNA damage. A phosphorylation mutant XRCC1 that eliminates PNKP binding fails to support efficient PNKP recruitment to microirradiation-induced damage. However, cells expressing this PNKP interaction mutant of XRCC1 show marked reversal of CPT hypersensitivity, revealing XRCC1-dependent repair that does not require phosphorylation-dependent PNKP recruitment. Stable expression of XRCC1 phosphorylation mutant in Xrcc1-/- mouse fibroblasts; PNKP-GFP microirradiation recruitment assay; clonogenic survival after CPT and H2O2 DNA repair High 29100039
2020 After replication stress, XRCC1 forms an active repair complex with POLQ and MRE11 that supports alternative end-joining (alt-EJ/MMEJ) activity in vitro. BRCA2 normally limits XRCC1 recruitment and complex formation to suppress alt-EJ at stalled forks. In BRCA2-deficient cells, XRCC1 enables replication completion via MRE11-dependent fork resection and restart at the expense of increased genome instability. In vitro alt-EJ reconstitution assay with XRCC1, POLQ, MRE11; Co-IP of XRCC1 with POLQ and MRE11; BRCA2 depletion in combination with XRCC1 depletion; replication fork restart and chromosome aberration assays NAR cancer Medium 32776008
2022 PARP1 and XRCC1 exhibit a reciprocal relationship: recruitment of either protein to DNA damage sites is impeded in the absence of the other in HeLa cells. In XRCC1 KO cells, hypersensitivity to CPT and impaired DNA repair can be partially rescued by additional deletion of PARP1, confirming that aberrant PARP1 activity drives toxicity in XRCC1-deficient cells. PARP1 KO, XRCC1 KO, and double KO HeLa cells; live-cell imaging of damage recruitment; NAD+ measurements; clonogenic survival; cell cycle and cell death analysis; comet assay Cell biology and toxicology High 35778544
1992 XRCC1 mRNA levels are substantially higher in testis (7–8 fold), ovary (3–4 fold), and brain (4–5 fold) compared to intestine, liver, and spleen, and high XRCC1 protein levels are detected in testis, suggesting a specialized role in DNA processing during meiogenesis and recombination. Northern blot analysis; tissue-specific mRNA quantification; Western blot for XRCC1 protein in rat tissues Biochemical and biophysical research communications Medium 1353960

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 XRCC1 and DNA strand break repair. DNA repair 502 12967653
1997 XRCC1 protein interacts with one of two distinct forms of DNA ligase III. Biochemistry 227 9136882
2016 XRCC1 mutation is associated with PARP1 hyperactivation and cerebellar ataxia. Nature 223 28002403
2011 Targeted therapy for advanced renal cell cancer (RCC): a Cochrane systematic review of published randomised trials. BJU international 212 21952069
2010 Xp11 translocation renal cell carcinoma (RCC): extended immunohistochemical profile emphasizing novel RCC markers. The American journal of surgical pathology 173 20679884
2004 XRCC1 co-localizes and physically interacts with PCNA. Nucleic acids research 163 15107487
2021 XRCC1 prevents toxic PARP1 trapping during DNA base excision repair. Molecular cell 161 34102106
2003 Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer letters 158 12565173
2019 XRCC1 protein; Form and function. DNA repair 139 31324530
2017 LncRNA-SARCC suppresses renal cell carcinoma (RCC) progression via altering the androgen receptor(AR)/miRNA-143-3p signals. Cell death and differentiation 137 28644440
2000 Molecular cloning, functional expression and characterisation of RCC reductase involved in chlorophyll catabolism. The Plant journal : for cell and molecular biology 117 10743659
2015 The structural basis of XRCC1-mediated DNA repair. DNA repair 111 25795425
2006 XRCC1 is phosphorylated by DNA-dependent protein kinase in response to DNA damage. Nucleic acids research 105 16397295
2015 The XRCC1 phosphate-binding pocket binds poly (ADP-ribose) and is required for XRCC1 function. Nucleic acids research 95 26130715
2014 HSP90 regulates DNA repair via the interaction between XRCC1 and DNA polymerase β. Nature communications 94 25423885
2002 Genetic polymorphisms of XRCC1 and risk of gastric cancer. Cancer letters 88 12359351
2021 Loss of Von Hippel-Lindau (VHL) Tumor Suppressor Gene Function: VHL-HIF Pathway and Advances in Treatments for Metastatic Renal Cell Carcinoma (RCC). International journal of molecular sciences 81 34575959
2008 XRCC1 and XRCC3 variants and risk of glioma and meningioma. Journal of neuro-oncology 77 18330515
2013 MicroRNA expression signatures of stage, grade, and progression in clear cell RCC. Cancer biology & therapy 75 24351440
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
2007 DNA repair polymorphisms XRCC1 and MGMT and risk of adult gliomas. Neuroepidemiology 60 17898525
2021 XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair. Nature cell biology 57 34811483
2022 STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 55 36445063
2018 KDM5B demethylates H3K4 to recruit XRCC1 and promote chemoresistance. International journal of biological sciences 55 29989047
2014 Cytoreductive nephrectomy in patients with metastatic non-clear-cell renal cell carcinoma (RCC). BJU international 54 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 53 15533591
2004 Biophysical characterization of human XRCC1 and its binding to damaged and undamaged DNA. Biochemistry 53 15610045
2010 XRCC1 phosphorylation by CK2 is required for its stability and efficient DNA repair. DNA repair 52 20471329
2005 Polymorphisms of XRCC1 gene, alcohol consumption and colorectal cancer. International journal of cancer 52 15800946
2019 SIRT1 deacetylated and stabilized XRCC1 to promote chemoresistance in lung cancer. Cell death & disease 51 31043584
2011 Polymorphisms of XRCC1 and gastric cancer susceptibility: a meta-analysis. Molecular biology reports 50 21604176
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
2021 Androgen receptor promotes renal cell carcinoma (RCC) vasculogenic mimicry (VM) via altering TWIST1 nonsense-mediated decay through lncRNA-TANAR. Oncogene 49 33510354
2020 XRCC1 promotes replication restart, nascent fork degradation and mutagenic DNA repair in BRCA2-deficient cells. NAR cancer 47 32776008
2015 A river model to map convergent cancer evolution and guide therapy in RCC. Nature reviews. Urology 46 26526752
2020 XRCC1 - Strategies for coordinating and assembling a versatile DNA damage response. DNA repair 45 33087283
2012 Epigenetic regulation in RCC: opportunities for therapeutic intervention? Nature reviews. Urology 42 22249190
2011 XRCC1 and base excision repair balance in response to nitric oxide. DNA repair 42 22041025
2007 Expression of renal cell carcinoma antigen (RCC) in renal epithelial and nonrenal tumors: diagnostic Implications. Applied immunohistochemistry & molecular morphology : AIMM 42 17721277
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
2010 Obesity, cholesterol, and clear-cell renal cell carcinoma (RCC). Advances in cancer research 41 20399960
2007 XRCC1 stimulates polynucleotide kinase by enhancing its damage discrimination and displacement from DNA repair intermediates. The Journal of biological chemistry 40 17650498
2007 Menopausal age and XRCC1 gene polymorphisms: role in breast cancer risk. Cancer detection and prevention 39 17935911
1992 Alterations in expression and structure of the DNA repair gene XRCC1. Biochemical and biophysical research communications 39 1353960
2011 The complex roles of Wnt antagonists in RCC. Nature reviews. Urology 38 22025172
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 38 19673050
2011 ERCC1 and XRCC1 as biomarkers for lung and head and neck cancer. Pharmacogenomics and personalized medicine 37 23226053
2008 XRCC1 polymorphism and lung cancer risk. Expert review of molecular diagnostics 37 18999926
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
2007 DNA repair gene XRCC1 polymorphisms and bladder cancer risk. BMC genetics 36 17425776
2019 SIRT1 downregulated FGB expression to inhibit RCC tumorigenesis by destabilizing STAT3. Experimental cell research 35 31201813
2019 Drug resistance in papillary RCC: from putative mechanisms to clinical practicalities. Nature reviews. Urology 32 31602010
2021 Renal cell carcinoma (RCC): fatter is better? A review on the role of obesity in RCC. Endocrine-related cancer 31 33949971
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
2019 PARP1 blockade is synthetically lethal in XRCC1 deficient sporadic epithelial ovarian cancers. Cancer letters 30 31669203
2013 Risk of infections in renal cell carcinoma (RCC) and non-RCC patients treated with mammalian target of rapamycin inhibitors. British journal of cancer 30 23736025
2005 DNA damage levels and biochemical repair capacities associated with XRCC1 deficiency. Biochemistry 29 16245950
1995 Expression of the DNA repair gene XRCC1 in baboon tissues. Mutation research 28 8524362
2021 Identification of RCC Subtype-Specific microRNAs-Meta-Analysis of High-Throughput RCC Tumor microRNA Expression Data. Cancers 27 33535553
2023 PRMT2 promotes RCC tumorigenesis and metastasis via enhancing WNT5A transcriptional expression. Cell death & disease 26 37173306
2016 Temporal activation of XRCC1-mediated DNA repair is essential for muscle differentiation. Cell discovery 25 27462438
2016 Rock2 promotes RCC proliferation by decreasing SCARA5 expression through β-catenin/TCF4 signaling. Biochemical and biophysical research communications 25 27793664
2012 MLH1 and XRCC1 polymorphisms in Mexican patients with colorectal cancer. Genetics and molecular research : GMR 24 22843073
2025 YTHDC1 lactylation regulates its phase separation to enhance target mRNA stability and promote RCC progression. Molecular cell 22 40680722
2021 Suppression of lncRNA HOTAIR alleviates RCC angiogenesis through regulating miR-126/EGFL7 axis. American journal of physiology. Cell physiology 22 33502949
2021 ALK-rearranged Renal Cell Carcinoma (RCC): A Report of 2 Cases and Review of the Literature Emphasizing the Distinction Between VCL-ALK and Non-VCL-ALK RCC. International journal of surgical pathology 22 33729862
2008 Characterization of plant XRCC1 and its interaction with proliferating cell nuclear antigen. Planta 22 18247046
2018 Differentiating papillary type I RCC from clear cell RCC and oncocytoma: application of whole-lesion volumetric ADC measurement. Abdominal radiology (New York) 21 29520425
2017 C1QBP Regulates YBX1 to Suppress the Androgen Receptor (AR)-Enhanced RCC Cell Invasion. Neoplasia (New York, N.Y.) 21 28107702
2011 Disconnecting XRCC1 and DNA ligase III. Cell cycle (Georgetown, Tex.) 21 21636980
2008 E2F1 regulates the base excision repair gene XRCC1 and promotes DNA repair. The Journal of biological chemistry 21 18348985
2018 Relationship between expression of XRCC1 and tumor proliferation, migration, invasion, and angiogenesis in glioma. Investigational new drugs 20 30328556
2008 New anti-angiogenic targeted therapy in advanced renal cell carcinoma (RCC): current status and future prospects. Reviews on recent clinical trials 20 18474019
2020 Circular RNA circMTO1 Suppresses RCC Cancer Cell Progression via miR9/LMX1A Axis. Technology in cancer research & treatment 19 32207384
2017 Recent advances in localized RCC: A focus on VEGF and immuno-oncology therapies. Urologic oncology 19 29051029
2017 Polymorphisms of DNA repair genes XRCC1 and LIG4 and idiopathic male infertility. Systems biology in reproductive medicine 18 28991497
2015 Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility. World journal of surgical oncology 18 26271249
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
2021 Stereotactic Ablative Radiation (SAbR) for Oligometastatic RCC. Seminars in radiation oncology 17 34090649
2019 Identification of an XRCC1 DNA binding activity essential for retention at sites of DNA damage. Scientific reports 17 30816207
2018 XRCC1 gene polymorphisms and risk of neuroblastoma in Chinese children. Aging 17 30362960
2018 Domain analysis of PNKP-XRCC1 interactions: Influence of genetic variants of XRCC1. The Journal of biological chemistry 17 30446622
2022 Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy. Cancer cell international 16 36510217
2020 XRCC1 Is a Promising Predictive Biomarker and Facilitates Chemo-Resistance in Gallbladder Cancer. Frontiers in molecular biosciences 16 32426369
2017 Polymorphisms and mutations in GSTP1, RAD51, XRCC1 and XRCC3 genes in breast cancer patients. The International journal of biological markers 16 28315507
2024 Predictive value of SIRI and SII for metastases in RCC: a prospective clinical study. BMC urology 15 38218876
2010 XRCC1, but not APE1 and hOGG1 gene polymorphisms is a risk factor for pterygium. Molecular vision 15 20577654
2023 The role of immune checkpoint inhibitors (ICI) as adjuvant treatment in renal cell carcinoma (RCC): A systematic review and meta-analysis. Clinical genitourinary cancer 14 36823017
2022 PARP1 and XRCC1 exhibit a reciprocal relationship in genotoxic stress response. Cell biology and toxicology 14 35778544
2022 Potential Value of Visfatin, Omentin-1, Nesfatin-1 and Apelin in Renal Cell Carcinoma (RCC): A Systematic Review and Meta-Analysis. Diagnostics (Basel, Switzerland) 14 36553076
2020 The influence of dysbiosis on kidney stones that risk up renal cell carcinoma (RCC). Seminars in cancer biology 14 32569823
2018 Haplotype analysis of XRCC1 gene polymorphisms and the risk of thyroid carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 14 29552790
2017 XRCC1-mediated repair of strand breaks independent of PNKP binding. DNA repair 14 29100039
2015 Efficacy and toxicity of sunitinib for non clear cell renal cell carcinoma (RCC): a systematic review of the literature. Critical reviews in oncology/hematology 14 25638704
2014 Association between XRCC1 polymorphisms and glioma risk among Chinese population. Medical oncology (Northwood, London, England) 14 25245010

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