Affinage

XRCC3

DNA repair protein XRCC3 · UniProt O43542

Length
346 aa
Mass
37.9 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: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XRCC3 is a RAD51-family paralog that operates as a core component of homologous recombination, executing error-free homology-directed repair of DNA double-strand breaks and maintaining chromosomal stability (PMID:9660962, PMID:10541549, PMID:11025669). It forms a stable heterodimeric complex with RAD51C in which the two subunits are mutually stabilizing — XRCC3 elevates RAD51C levels and, reciprocally, XRCC3 protein stability depends on heterodimerization with RAD51C (PMID:11842112, PMID:15292210). Within this complex XRCC3 is essential for single-stranded DNA binding while RAD51C provides the catalytic activity, and the reconstituted complex catalyzes homologous pairing and forms filamentous protein–DNA structures (PMID:11459987, PMID:11331762). Functionally, XRCC3 acts upstream of RAD51 nucleoprotein filament assembly: it is required for the formation of damage-induced RAD51 subnuclear foci and localizes to DNA breaks independently of RAD51, consistent with priming RAD51 loading at resected ends (PMID:9705276, PMID:15372620). XRCC3's ATPase activity (Walker A motif K113) is essential for recombinational repair and for suppression of long-tract gene conversion during sister chromatid recombination, with ATP binding/hydrolysis dynamically regulating RAD51C–XRCC3 complex formation (PMID:15037616, PMID:19470754). The complex governs replication fork progression on damaged templates and co-fractionates with Holliday junction resolvase activity, generating recombination intermediates that are processed downstream by BLM–Top3α (PMID:12718895, PMID:17114795, PMID:17923529). ATR/ATM-dependent phosphorylation of XRCC3 at Ser225, which requires RAD51C, controls RAD51 chromatin loading, intra-S checkpoint activation, and recovery of collapsed replication forks (PMID:23438602). XRCC3 additionally participates in a BRCA2–FANCD2–FANCG–XRCC3 complex assembled via FANCG Ser7 phosphorylation for crosslink repair, and the RAD51C/XRCC3 complex carries a nucleus-independent role at the mitochondrial D-loop, where Twinkle-dependent recruitment maintains POLG stability and mtDNA integrity under replication stress (PMID:18212739, PMID:29158291). A co-crystal structure of the RAD51C–XRCC3 heterodimer with bound ATP analog defines its ATP-binding mode and a polymerization motif, and maps separable replication fork protection, restart, and reversal functions (PMID:37488098).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1998 High

    Established XRCC3 as a RAD51-family member that physically engages RAD51 and rescues the DNA-damage sensitivity of a mutant cell line, placing it in the recombinational repair machinery.

    Evidence Sequence alignment, functional complementation of irs1SF hamster cells, and direct interaction assay with HsRad51

    PMID:9660962

    Open questions at the time
    • Did not define a biochemical activity for XRCC3 itself
    • Stoichiometry and direct binding partners beyond RAD51 unresolved
  2. 1998 High

    Showed XRCC3 acts upstream of RAD51 assembly by demonstrating it is required for damage-induced RAD51 focus formation.

    Evidence Immunofluorescence of RAD51 foci in irs1SF cells with and without XRCC3 complementation after IR or cisplatin

    PMID:9705276

    Open questions at the time
    • Mechanism of how XRCC3 promotes focus assembly not defined
    • Direct versus indirect role unresolved at this stage
  3. 1999 High

    Quantified XRCC3's contribution as essential for error-free homology-directed repair of double-strand breaks.

    Evidence Fluorescence-based HDR assay showing 25-fold reduction in XRCC3-deficient cells, restored by complementation

    PMID:10541549 PMID:10725659

    Open questions at the time
    • Step in HDR pathway requiring XRCC3 not pinpointed
    • Did not address mitotic or checkpoint consequences
  4. 2000 High

    Connected loss of XRCC3 to genome instability beyond repair failure, linking unresolved DNA damage to chromosome missegregation and centrosome fragmentation.

    Evidence Cytogenetic analysis of chromosome segregation and centrosome morphology in XRCC3-null cells

    PMID:11025669

    Open questions at the time
    • Causal chain from repair defect to centrosome amplification not mechanistically dissected
  5. 2001 High

    Reconstituted the RAD51C–XRCC3 heterodimer biochemically and assigned subunit roles — XRCC3 confers ssDNA binding, RAD51C is catalytic — and showed the complex catalyzes homologous pairing.

    Evidence Baculovirus co-expression, co-purification, co-IP from HeLa, EM, DNA-binding and in vitro homologous pairing assays

    PMID:11331762 PMID:11459987

    Open questions at the time
    • How homologous pairing activity relates to RAD51 loading in cells not resolved
    • Regulation of complex activity unknown
  6. 2002 High

    Defined XRCC3's place within the paralog network as part of a discrete RAD51C–XRCC3 complex distinct from the RAD51B–RAD51C–RAD51D–XRCC2 complex, with mutual subunit stabilization.

    Evidence Reciprocal His-tag pull-downs and Western blotting in stable human cell lines

    PMID:11842112

    Open questions at the time
    • Functional division of labor between the two paralog complexes not established
  7. 2002 High

    Tested the cancer-associated Thr241Met polymorphism functionally and found it HDR-proficient, separating disease association from intrinsic repair disruption.

    Evidence Quantitative HDR assay and MMC sensitivity in complemented XRCC3-mutant cells

    PMID:12037675

    Open questions at the time
    • Non-HDR routes by which the variant might contribute to cancer not addressed here
  8. 2003 High

    Demonstrated a replication-associated function: the RAD51C–XRCC3 complex modulates fork progression on damaged templates, with the defect rescued by purified complex and bypassed by RAD51.

    Evidence DNA fiber analysis and in vitro replication in permeabilized CHO and DT40 cells with purified complex addition

    PMID:12718895

    Open questions at the time
    • Molecular event at the fork requiring XRCC3 not defined
    • Relationship to RAD51 loading at forks unresolved
  9. 2004 High

    Identified XRCC3 ATPase activity (Walker A K113) as essential for repair and as a regulator of complex dynamics, with ATP binding modulating RAD51C–XRCC3 association.

    Evidence Walker A mutagenesis (K113A/K113R), mammalian complementation, bacterial co-expression and purification

    PMID:15037616

    Open questions at the time
    • How ATP-driven dynamics couple to RAD51 loading in vivo not shown
    • Catalytic versus structural role of hydrolysis not fully separated
  10. 2004 Medium

    Showed XRCC3 localizes to breaks within minutes independently of RAD51, supporting a model where it associates with DNA breaks before facilitating RAD51 filament assembly; and confirmed XRCC3 stability depends on RAD51C.

    Evidence Immunofluorescence of XRCC3 foci with RAD51 RNAi; siRNA depletion of RAD51C with Western, HR, and survival readouts

    PMID:15292210 PMID:15372620

    Open questions at the time
    • RAD51-independent recruitment shown by single method (idx 11)
    • Recruitment receptor at breaks not identified
  11. 2006 High

    Linked the complex to resolution of recombination intermediates by showing co-elution with Holliday junction resolvase activity.

    Evidence IP, gel filtration, HJ resolvase assay, and meiotic chromosome immunofluorescence

    PMID:17114795

    Open questions at the time
    • Whether XRCC3/RAD51C is the resolvase or an associated factor not resolved
    • Identity of catalytic resolvase activity not assigned
  12. 2006 Medium

    Dissected two XRCC3 variants to show HR proficiency and mitotic surveillance are separable, with T241M increasing centrosome/binucleation defects without triggering apoptosis.

    Evidence HR complementation, centrosome counting, binucleation and apoptosis assays for D213N and T241M variants

    PMID:16505003

    Open questions at the time
    • Single-lab variant phenotyping
    • Mechanism linking XRCC3 to apoptotic elimination of aberrant cells not defined
  13. 2006 High

    Positioned XRCC3 in a branched RAD51-loading pathway by showing synthetic lethality with γH2AX, with each acting through a separate arm.

    Evidence DT40 double mutants (XRCC3−/−/H2AX−), clonogenic survival, RAD51 focus and aberration analysis with conditional rescue

    PMID:17123873

    Open questions at the time
    • Molecular distinction between the two RAD51-loading arms not fully defined
  14. 2007 High

    Placed XRCC3 upstream of BLM–Top3α by showing XRCC3 generates recombination intermediates that BLM resolves to suppress sister chromatid exchange.

    Evidence DT40 double/triple mutant epistasis, SCE assay, survival and chromosomal aberration analysis

    PMID:17923529

    Open questions at the time
    • Nature of the XRCC3-generated intermediate not biochemically defined
  15. 2008 High

    Embedded XRCC3 in the Fanconi crosslink-repair axis via a phospho-dependent BRCA2–FANCD2–FANCG–XRCC3 complex.

    Evidence Co-IP from human and hamster cells, FANCG pSer7 phospho-mutant constructs, DT40 epistasis with crosslinkers

    PMID:18212739

    Open questions at the time
    • Direct XRCC3 contact within the complex not mapped
    • How this complex couples to HR machinery not defined
  16. 2013 High

    Identified XRCC3 Ser225 as an ATR/ATM-pathway phosphosite (RAD51C-dependent) controlling RAD51 chromatin loading, the intra-S checkpoint, and collapsed-fork recovery, separating these from a phosphorylation-independent G2/M checkpoint role.

    Evidence Phospho-specific antibodies, kinase inhibitors, S225A mutagenesis, siRNA, HR, checkpoint and fork recovery assays

    PMID:23438602

    Open questions at the time
    • Direct reader of phospho-Ser225 not identified
    • Structural consequence of phosphorylation not defined
  17. 2013 Medium

    Revealed redox regulation: XRCC3 cysteines are reversibly oxidized by ROS and required for HR/camptothecin resistance, with oxidative stress driving chromatin relocalization.

    Evidence Non-reducing SDS-PAGE, glutathione depletion, Cys→Ser mutagenesis, fractionation, immunofluorescence, clonogenic survival

    PMID:24116071

    Open questions at the time
    • Single-lab study
    • Physiological context where cysteine oxidation regulates XRCC3 not established
  18. 2018 High

    Uncovered a nucleus-independent mitochondrial role: Twinkle-dependent recruitment of RAD51C/XRCC3 to the mtDNA D-loop maintains POLG stability and mtDNA integrity under replication stress.

    Evidence Subcellular fractionation, ChIP on mtDNA, siRNA, mtDNA synthesis and lesion assays, co-IP with POLG and Twinkle

    PMID:29158291

    Open questions at the time
    • Whether mitochondrial function uses HR-like activity not resolved
    • Direct XRCC3 contribution versus RAD51C not separated
  19. 2023 High

    Provided the structural basis for XRCC3 function — a RAD51C–XRCC3 co-crystal with bound ATP analog revealing the ATP-binding mode, complex interfaces, and a polymerization motif, with mapping of separable fork protection/restart/reversal functions.

    Evidence X-ray crystallography, CRISPR editing, single-molecule and single-cell assays, biophysics, HDR analysis

    PMID:37488098

    Open questions at the time
    • Structure of the complex engaged with DNA or RAD51 filament not resolved
    • Implied 5′ filament capping activity not directly visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XRCC3's distinct activities — nuclear HR, replication fork protection, crosslink repair, and mitochondrial genome maintenance — are coordinated, and what directly reads its regulatory modifications, remains open.
  • No reader of phospho-Ser225 identified
  • Structural picture of DNA/RAD51-engaged complex lacking
  • Coupling of mitochondrial and nuclear roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0140657 ATP-dependent activity 3 GO:0003677 DNA binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1 GO:0005829 cytosol 1
Pathway
R-HSA-73894 DNA Repair 4 R-HSA-1640170 Cell Cycle 3 R-HSA-69306 DNA Replication 3 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
BRCA2FANCD2FANCGPOLGRAD51RAD51CTWNK
Complex memberships
BRCA2–FANCD2–FANCG–XRCC3RAD51C–XRCC3 (CX3) heterodimermitochondrial D-loop nucleoid complex (with POLG/Twinkle)

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 XRCC3 is a member of the RAD51 gene family and interacts directly with HsRad51, complementing the DNA damage sensitivity and chromosomal instability of irs1SF hamster cells. Sequence alignment, functional complementation, direct protein interaction assay Molecular cell High 9660962
1998 Xrcc3 is required for the assembly or stabilization of damage-induced Rad51 subnuclear foci in CHO cells; irs1SF cells lacking Xrcc3 fail to form Rad51 foci after ionizing radiation or cisplatin, and this defect is corrected by Xrcc3 expression. Immunofluorescence microscopy of Rad51 foci in irs1SF cells with and without Xrcc3 complementation The Journal of biological chemistry High 9705276
1999 XRCC3 promotes error-free homology-directed repair (HDR) of DNA double-strand breaks in mammalian cells; XRCC3-deficient hamster cells show a 25-fold decrease in HDR, restored to wild-type by XRCC3 expression. Fluorescence-based HDR assay in XRCC3-deficient irs1SF cells with and without XRCC3 complementation Genes & development High 10541549
2000 XRCC3 is required for efficient homologous recombinational repair (HRR) of chromosomal double-strand breaks; transient complementation of irs1SF cells with XRCC3 increased HRR frequency 34- to 260-fold. DSB-induced HRR assay in irs1SF cells with transient XRCC3 expression Mutation research High 10725659
2000 Loss of XRCC3 (or XRCC2) causes highly significant increases in chromosome missegregation associated with centrosome fragmentation, indicating that unresolved DNA damage triggers this instability. Cytogenetic analysis of chromosome segregation and centrosome morphology in XRCC3-deficient cell lines Nature cell biology High 11025669
2001 Human RAD51C and XRCC3 form a stable heterodimeric complex that co-purifies from baculovirus-infected insect cells and from HeLa cell extracts; the purified RAD51C–XRCC3 complex binds single-stranded but not duplex DNA, forming protein–DNA networks visible by electron microscopy. Baculovirus co-expression, co-purification, co-immunoprecipitation from HeLa cells, electron microscopy, DNA-binding assay Proceedings of the National Academy of Sciences of the United States of America High 11459987
2001 The purified Xrcc3·Rad51C complex catalyzes homologous pairing in vitro; Xrcc3 is essential for the DNA-binding activity of the complex, while Rad51C is the catalytic subunit. The complex forms filamentous structures with ssDNA visible by electron microscopy. Yeast two-hybrid with brain cDNA library, baculovirus purification of Xrcc3·Rad51C, in vitro homologous pairing assay, DNA-binding assay, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 11331762
2002 XRCC3 and RAD51C interact in human cells; RAD51C, but not XRCC3, also interacts with RAD51B, RAD51D, and XRCC2, establishing two distinct paralog complexes: RAD51C–XRCC3 and RAD51B–RAD51C–RAD51D–XRCC2. Rad51 is not found in either complex. Overexpression of XRCC3 moderately elevates endogenous RAD51C, suggesting dimerization stabilizes RAD51C. Stable human cell lines expressing His-tagged XRCC3 or RAD51C; Ni2+-affinity pull-down; Western blotting Nucleic acids research High 11842112
2002 The XRCC3 variant Thr241Met is functionally active for homology-directed repair and does not confer hypersensitivity to mitomycin C, indicating that the cancer-associated polymorphism does not intrinsically disrupt HDR function. Quantitative fluorescence HDR assay; MMC sensitivity assay in XRCC3-mutant cells expressing wild-type or Thr241Met variant Oncogene High 12037675
2003 XRCC3 and Rad51 cooperatively modulate replication fork progression on damaged vertebrate chromosomes; fork slowing after cisplatin or UV is absent in irs1SF and XRCC3−/− DT40 cells, restored by addition of purified human Rad51C–XRCC3 complex to permeabilized cells, and bypassed by addition of Rad51. DNA fiber analysis; in vitro replication assay in permeabilized cells; addition of purified Rad51C–XRCC3 complex; chicken DT40 and CHO cell genetics Molecular cell High 12718895
2004 XRCC3 ATPase activity (Walker A motif, K113) is essential for homologous recombinational repair; ATPase mutants (K113A and K113R) fail to complement irs1SF cells. The K113A mutant still forms a stable complex with Rad51C, whereas K113R does not. Addition of ATP (but not ADP) abolishes wild-type Rad51C–XRCC3 complex formation in vitro, indicating that ATP binding/hydrolysis regulates complex dynamics. Site-directed mutagenesis of Walker A box; mammalian complementation assay; bacterial co-expression with Ni-affinity purification; Western blotting The Journal of biological chemistry High 15037616
2004 XRCC3 localizes to sites of DNA damage in human cells as distinct foci within 10 minutes of radiation treatment, independently of Rad51 (RNAi knockdown of Rad51 does not prevent Xrcc3 focus formation), consistent with a model in which Xrcc3 associates directly with DNA breaks before facilitating Rad51 nucleoprotein filament assembly. Immunofluorescence microscopy of Xrcc3 foci; RNAi-mediated Rad51 knockdown; live-cell and fixed-cell imaging Journal of cellular biochemistry Medium 15372620
2004 Depletion of Rad51C by siRNA in human cells reduces XRCC3 protein levels, demonstrating that XRCC3 stability depends on heterodimerization with Rad51C. Rad51C depletion also reduces homologous recombination frequency and causes MMC hypersensitivity and cell-cycle-phase-specific (S and G2/M) radiosensitivity. siRNA knockdown; Western blotting; HR frequency assay; clonogenic survival; cell cycle analysis The Journal of biological chemistry High 15292210
2006 The RAD51C–XRCC3 complex (80 kDa) co-elutes with Holliday junction resolvase activity by gel filtration and co-immunoprecipitation, indicating that the complex is associated with resolution of recombination intermediates prior to chromosome segregation. Immunoprecipitation; gel filtration; Holliday junction resolvase activity assay; mouse meiotic chromosome immunofluorescence The Journal of biological chemistry High 17114795
2006 XRCC3 variant D213N is defective in homologous recombination and causes increased apoptosis of cells with mitotic defects (elevated centrosome number, binucleated cells), whereas T241M is proficient in HR but also increases centrosome number/binucleation without inducing apoptosis, suggesting T241M may promote cancer by failing to eliminate mitotically aberrant cells. HR assay (MMC sensitivity complementation); centrosome counting; binucleation assay; apoptosis measurement in cells expressing XRCC3 variants Human molecular genetics Medium 16505003
2006 XRCC3 deletion in DT40 cells and γH2AX mutation are synthetically lethal; both independently delay Rad51 focus formation after IR through separate arms of a branched pathway for Rad51 assembly at DSBs. Chicken DT40 double-mutant generation (XRCC3−/−/H2AX−/S139A); clonogenic survival; Rad51 focus formation; chromosomal aberration analysis; conditional transgene rescue DNA repair High 17123873
2007 XRCC3 activity generates recombination intermediates (substrates) that give rise to elevated sister chromatid exchanges (SCE) in BLM-deficient cells; BLM with Top3α acts downstream of XRCC3 to suppress SCE formation. Disruption of XRCC3 also suppresses MMS/UV sensitivity and chromosomal aberrations of blm cells. DT40 double/triple mutant genetics; SCE assay; clonogenic survival; chromosomal aberration analysis The Journal of cell biology High 17923529
2008 FANCG promotes formation of a protein complex containing BRCA2 (FANCD1), FANCD2, FANCG, and XRCC3 (D1-D2-G-X3); phosphorylation of FANCG serine 7 is required for co-precipitation of BRCA2, XRCC3, and FANCD2, and for direct BRCA2–FANCD2 interaction. FANCG and XRCC3 are epistatic for sensitivity to DNA crosslinking agents in DT40 cells. Co-immunoprecipitation from human and hamster cells; phospho-mutant FANCG constructs; DT40 epistasis analysis Oncogene High 18212739
2009 XRCC3-mediated homologous recombination and suppression of long-tract gene conversion (LTGC) during sister chromatid recombination are dependent on ATP binding and hydrolysis by XRCC3, whereas the analogous XRCC2 function does not require ATP binding/hydrolysis. Sister chromatid recombination assay in hamster cells; XRCC3 Walker motif mutants; quantification of short-tract vs. long-tract gene conversion Molecular and cellular biology High 19470754
2013 ATR kinase phosphorylates XRCC3 at serine 225 (SQ motif) in an ATM-dependent signaling context; this phosphorylation requires RAD51C but not XRCC2, occurs after end resection specifically in S and G2 phases, and is required for chromatin loading of RAD51 and HR-mediated DSB repair. XRCC3 phosphorylation is also required for intra-S-phase checkpoint activation and for HR-mediated recovery of collapsed (but not stalled) replication forks; XRCC3 participates in the G2/M checkpoint independently of its phosphorylation. Phospho-specific antibodies; kinase inhibitors; phospho-site mutagenesis (S225A); siRNA; HR assay; checkpoint and replication fork recovery assays Molecular and cellular biology High 23438602
2013 XRCC3 cysteine residues are oxidized by ROS (UVA, various oxidants) in mammalian cells, causing increased electrophoretic mobility; oxidation is rapidly reversed by cellular reducing systems. XRCC3 localizes to both cytoplasm and nucleus; mutating all cysteines to serines does not affect localization but confers sensitivity to camptothecin (HR defect), while oxidative stress induces chromatin relocalization of both wild-type and cysteine mutant XRCC3. Non-reducing SDS-PAGE; glutathione depletion; site-directed mutagenesis (Cys→Ser); subcellular fractionation; immunofluorescence; clonogenic survival PloS one Medium 24116071
2018 RAD51C/XRCC3 localizes to mitochondria and to the mitochondrial D-loop nucleoid region; this recruitment depends on Twinkle helicase. Absence of RAD51C/XRCC3 reduces POLG stability on mtDNA, decreases mtDNA synthesis, and increases mtDNA lesions under replication stress, establishing a nucleus-independent role in mitochondrial genome maintenance. Subcellular fractionation; chromatin immunoprecipitation on mtDNA; siRNA knockdown; mtDNA synthesis assay; mtDNA lesion quantification; co-immunoprecipitation with POLG and Twinkle Molecular and cellular biology High 29158291
2023 X-ray co-crystal structure of the RAD51C–XRCC3 (CX3) heterodimer with bound ATP analog reveals ATP-binding mode matching RAD51 recombinase, distinct CX3 interfaces, and an unappreciated polymerization motif. Cancer patient mutations mapped onto the structure define separable RAD51C functions: CX3 has discrete regions for DNA replication fork protection, restart, and reversal accomplished by separable DNA-binding and implied 5′ RAD51 filament capping activities. X-ray crystallography; CRISPR/Cas9 editing of human cells; single-molecule and single-cell assays; biophysics measurements; HDR functional analysis Nature communications High 37488098

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. Genes & development 1174 10541549
1998 XRCC2 and XRCC3, new human Rad51-family members, promote chromosome stability and protect against DNA cross-links and other damages. Molecular cell 456 9660962
2001 XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis 404 11532866
1998 Xrcc3 is required for assembly of Rad51 complexes in vivo. The Journal of biological chemistry 234 9705276
2000 A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer. Cancer research 227 11059748
2000 Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nature cell biology 196 11025669
2006 XRCC3 and XPD/ERCC2 single nucleotide polymorphisms and the risk of cancer: a HuGE review. American journal of epidemiology 166 16707649
2003 Polymorphisms of XRCC1 and XRCC3 genes and susceptibility to breast cancer. Cancer letters 158 12565173
2000 XRCC3 is required for efficient repair of chromosome breaks by homologous recombination. Mutation research 149 10725659
2003 XRCC3 and Rad51 modulate replication fork progression on damaged vertebrate chromosomes. Molecular cell 139 12718895
2001 Complex formation by the human RAD51C and XRCC3 recombination repair proteins. Proceedings of the National Academy of Sciences of the United States of America 111 11459987
2001 Homologous-pairing activity of the human DNA-repair proteins Xrcc3.Rad51C. Proceedings of the National Academy of Sciences of the United States of America 108 11331762
1999 The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells. Mutation research 107 10422536
2004 Are genetic polymorphisms in OGG1, XRCC1 and XRCC3 genes predictive for the DNA strand break repair phenotype and genotoxicity in workers exposed to low dose ionising radiations? Mutation research 101 15491645
2002 Interactions involving the Rad51 paralogs Rad51C and XRCC3 in human cells. Nucleic acids research 97 11842112
2002 Variant XRCC3 implicated in cancer is functional in homology-directed repair of double-strand breaks. Oncogene 96 12037675
2006 Role of RAD51C and XRCC3 in genetic recombination and DNA repair. The Journal of biological chemistry 92 17114795
2002 DNA repair gene XRCC3 codon 241 polymorphism, its interaction with smoking and XRCC1 polymorphisms, and bladder cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 85 12223443
2004 DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract. International journal of cancer 79 15386379
2008 XRCC1 and XRCC3 variants and risk of glioma and meningioma. Journal of neuro-oncology 77 18330515
2008 Polymorphisms of the DNA repair genes XRCC1 and XRCC3 and risk of lung and colorectal cancer: a case-control study in a Southern Italian population. Anticancer research 77 19031937
2006 DNA repair gene XRCC3 polymorphisms and cancer risk: a meta-analysis of 48 case-control studies. European journal of human genetics : EJHG 77 16791138
2004 Polymorphisms XRCC1-R399Q and XRCC3-T241M and the risk of breast cancer at the Ontario site of the Breast Cancer Family Registry. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 75 15066923
2008 FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. Oncogene 69 18212739
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
2005 Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms. Mutagenesis 62 16234265
2007 XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. The American journal of gastroenterology 60 17986315
2013 ATM- and ATR-mediated phosphorylation of XRCC3 regulates DNA double-strand break-induced checkpoint activation and repair. Molecular and cellular biology 58 23438602
2007 hOGG1(326), XRCC1(399) and XRCC3(241) polymorphisms influence micronucleus frequencies in human lymphocytes in vivo. Mutagenesis 58 17971348
2009 Bladder cancer and polymorphisms of DNA repair genes (XRCC1, XRCC3, XPD, XPG, APE1, hOGG1). Anticancer research 56 19414392
2009 Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population? Mutation research 52 19815090
2007 Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma. Human molecular genetics 52 17901044
2004 Human Rad51C deficiency destabilizes XRCC3, impairs recombination, and radiosensitizes S/G2-phase cells. The Journal of biological chemistry 51 15292210
2009 XRCC2 and XRCC3 regulate the balance between short- and long-tract gene conversions between sister chromatids. Molecular and cellular biology 50 19470754
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
2009 Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists. Mutation research 49 19393248
2010 Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case-control study in an Indian population. Journal of cancer research and clinical oncology 48 20229274
2012 Genetic polymorphisms of DNA repair genes XRCC1 and XRCC3 and risk of colorectal cancer in Chinese population. Asian Pacific journal of cancer prevention : APJCP 47 22524842
2008 DNA repair gene ERCC2, XPC, XRCC1, XRCC3 polymorphisms and associations with bladder cancer risk in a French cohort. Anticancer research 47 18630471
2002 A variant of the DNA repair gene XRCC3 and risk of squamous cell carcinoma of the head and neck: a case-control analysis. International journal of cancer 47 12115490
2004 Xrcc3 is recruited to DNA double strand breaks early and independent of Rad51. Journal of cellular biochemistry 46 15372620
2006 No association between XRCC1 and XRCC3 gene polymorphisms and breast cancer risk: Iowa Women's Health Study. Cancer detection and prevention 45 16963196
2004 Polymorphisms of DNA repair gene XRCC3 Thr241Met and risk of gastric cancer in a Chinese population. Cancer letters 44 15019159
2010 Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population. Experimental and molecular pathology 43 20804747
2018 RAD51C/XRCC3 Facilitates Mitochondrial DNA Replication and Maintains Integrity of the Mitochondrial Genome. Molecular and cellular biology 42 29158291
2013 XRCC3 Thr241Met gene polymorphisms and lung cancer risk: a meta-analysis. Journal of experimental & clinical cancer research : CR 42 23289442
2006 XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 42 17164360
2013 The relationship between XRCC1 and XRCC3 gene polymorphisms and lung cancer risk in northeastern Chinese. PloS one 41 23409158
1998 Increased expression of human DNA repair genes, XRCC1, XRCC3 and RAD51, in radioresistant human KB carcinoma cell line N10. Oral oncology 41 9930366
2009 XRCC3 Thr241Met polymorphism and breast cancer risk: a meta-analysis. Breast cancer research and treatment 39 19789975
2006 Collaborative roles of gammaH2AX and the Rad51 paralog Xrcc3 in homologous recombinational repair. DNA repair 38 17123873
2005 The association of the DNA repair gene XRCC3 Thr241Met polymorphism with susceptibility to colorectal cancer in a Chinese population. Cancer genetics and cytogenetics 38 16271954
2008 The polymorphism of XRCC3 codon 241 and AFB1-related hepatocellular carcinoma in Guangxi population, China. Annals of epidemiology 37 18504145
2004 An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. Journal of experimental & clinical cancer research : CR 37 15354414
2005 XRCC1 and XRCC3 polymorphisms and their role as effect modifiers of unsaturated fatty acids and antioxidant intake on colorectal adenomas risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 35 15767338
2011 Gene variants of XRCC4 and XRCC3 and their association with risk for urothelial bladder cancer. Molecular biology reports 34 21617942
2012 Genetic variability of Xrcc3 and Rad51 modulates the risk of head and neck cancer. Gene 33 22613844
2023 RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles. Nature communications 32 37488098
2006 Mitotic defects in XRCC3 variants T241M and D213N and their relation to cancer susceptibility. Human molecular genetics 32 16505003
2018 XRCC3 contributes to temozolomide resistance of glioblastoma cells by promoting DNA double-strand break repair. Cancer letters 31 29574277
2012 Allelic variants of XRCC1 and XRCC3 repair genes and susceptibility of oral cancer in Brazilian patients. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 31 22775506
2015 A systematic gene-gene and gene-environment interaction analysis of DNA repair genes XRCC1, XRCC2, XRCC3, XRCC4, and oral cancer risk. Omics : a journal of integrative biology 30 25831063
2011 RAD51 and XRCC3 gene polymorphisms and the risk of developing acute myeloid leukemia. Journal of investigative medicine : the official publication of the American Federation for Clinical Research 29 21725251
2011 Association between the XRCC3 polymorphisms and breast cancer risk: meta-analysis based on case-control studies. Molecular biology reports 29 22161248
2010 Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population. DNA and cell biology 29 20590474
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
2016 Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix. Oncotarget 28 27683114
2013 XRCC3 and RAD51 expression are associated with clinical factors in breast cancer. PloS one 27 23977219
2011 Combined effect of polymorphisms in Rad51 and Xrcc3 on breast cancer risk and chromosomal radiosensitivity. Molecular medicine reports 27 21725594
2008 Susceptibility of XRCC3, XPD, and XPG genetic variants to cervical carcinoma. Pathobiology : journal of immunopathology, molecular and cellular biology 27 19096231
2015 XRCC3 is essential for proper double-strand break repair and homologous recombination in rice meiosis. Journal of experimental botany 26 26034131
2014 XRCC3 C18067T polymorphism contributes a decreased risk to both basal cell carcinoma and squamous cell carcinoma: evidence from a meta-analysis. PloS one 26 24454720
2015 DNA repair genes XPC, XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck. DNA repair 25 26001739
2014 Association of DNA repair genes XRCC1 (Arg399Gln), (Arg194Trp) and XRCC3 (Thr241Met) polymorphisms with the risk of breast cancer: a case-control study in Egypt. Genetic testing and molecular biomarkers 25 25340946
2013 DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia. Biological research 25 23959014
2011 Genetic risk of DNA repair gene polymorphisms (XRCC1 and XRCC3) for high risk human papillomavirus negative cervical cancer in Northeast Thailand. Asian Pacific journal of cancer prevention : APJCP 25 21790234
2013 XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk. Pathology oncology research : POR 24 23539294
2003 XRCC3 genetic polymorphism, smoking, and lung carcinoma risk in minority populations. Cancer 24 14534887
2015 Association between XRCC1 and XRCC3 gene polymorphisms and risk of thyroid cancer. International journal of clinical and experimental pathology 23 26045834
2014 Contribution of DNA double-strand break repair gene XRCC3 genotypes to oral cancer susceptibility in Taiwan. Anticancer research 23 24922659
2012 Variation in DNA repair gene XRCC3 affects susceptibility to astrocytomas and glioblastomas. Genetics and molecular research : GMR 23 22370935
2004 XRCC3 ATPase activity is required for normal XRCC3-Rad51C complex dynamics and homologous recombination. The Journal of biological chemistry 23 15037616
2017 Association between the DNA Repair Gene XRCC3 rs861539 Polymorphism and Risk of Osteosarcoma: a Systematic Review and Meta-Analysis. Asian Pacific journal of cancer prevention : APJCP 22 28345844
2016 Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and ovarian cancer in Polish women. Experimental and molecular pathology 22 26801223
2015 RAD51, XRCC3, and XRCC2 mutation screening in Finnish breast cancer families. SpringerPlus 22 25918678
2015 XRCC3 is a promising target to improve the radiotherapy effect of esophageal squamous cell carcinoma. Cancer science 22 26383967
2013 Oxidative stress in mammalian cells impinges on the cysteines redox state of human XRCC3 protein and on its cellular localization. PloS one 22 24116071
2012 Association of XRCC3 and XPD751 SNP with efficacy of platinum-based chemotherapy in advanced NSCLC patients. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 22 22374424
2015 Association between Single Nucleotide Polymorphisms in XRCC3 and Radiation-Induced Adverse Effects on Normal Tissue: A Meta-Analysis. PloS one 21 26091483
2014 Analyzing association of the XRCC3 gene polymorphism with ovarian cancer risk. BioMed research international 21 25006581
2016 Correlation between gene polymorphisms of CYP1A1, GSTP1, ERCC2, XRCC1, and XRCC3 and susceptibility to lung cancer. Genetics and molecular research : GMR 20 27819744
2015 Contribution of DNA Double-strand Break Repair Gene XRCC3 Genotypes to Triple-negative Breast Cancer Risk. Cancer genomics & proteomics 20 26543082
2012 DNA repair gene XRCC3 T241M polymorphism and bladder cancer risk in a Chinese population. Genetic testing and molecular biomarkers 20 22299591
2017 Haplotype Based Analysis of XRCC3 Gene Polymorphisms in Thyroid Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 19 28490032
2014 Association of RAD 51 135 G/C, 172 G/T and XRCC3 Thr241Met gene polymorphisms with increased risk of head and neck cancer. Asian Pacific journal of cancer prevention : APJCP 19 25556492
2013 Quantitative assessment of the associations between DNA repair gene XRCC3 Thr241Met polymorphism and gastric cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 24197974
2012 Association between XRCC1 and XRCC3 polymorphisms and colorectal cancer risk: a meta-analysis of 23 case-control studies. Molecular biology reports 19 23271134
2007 Functional interactions between BLM and XRCC3 in the cell. The Journal of cell biology 19 17923529
2016 Polymorphisms in DNA Repair Gene XRCC3 and Susceptibility to Breast Cancer in Saudi Females. BioMed research international 18 26881229
2010 Relationship between XRCC3 T241M polymorphism and gastric cancer risk: a meta-analysis. Medical oncology (Northwood, London, England) 18 20549576

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