Affinage

XRCC2

DNA repair protein XRCC2 · UniProt O43543

Length
280 aa
Mass
32.0 kDa
Annotated
2026-06-11
100 papers in source corpus 29 papers cited in narrative 29 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

XRCC2 is a RecA/RAD51-family recombination-repair protein that is essential for homologous recombination (HR) repair of DNA double-strand breaks and for genome stability, with its loss causing >100-fold reduction in HR while leaving non-homologous end joining intact (PMID:9628903, PMID:9660962, PMID:10517641). It functions as a stable subunit of the multimeric RAD51 paralog complexes: it forms a direct, ATPase-active complex with RAD51D (PMID:10871607) and is a component of the BCDX2 heterotetramer (RAD51B-RAD51C-RAD51D-XRCC2) that preferentially binds branched DNA and catalyzes strand annealing (PMID:15141025). Cryo-EM resolves how these complexes act on RAD51 filaments: within BCDX2 the RAD51C-RAD51D-XRCC2 module mimics three RAD51 protomers to stimulate ATP-hydrolysis-dependent filament nucleation and extension on ssDNA, whereas the XRCC3-containing complex (XRCC3-RAD51C-RAD51D-XRCC2) caps 5' filament termini to promote homologous pairing (PMID:37344587, PMID:41196948). Mechanistically, XRCC2 is required for damage-induced RAD51 focus formation and chromatin loading without itself requiring ATP binding, distinguishing its role from the ATP-dependent activity of XRCC3 (PMID:11301337, PMID:12488590, PMID:19470754). Beyond canonical HR, XRCC2 acts late in the Fanconi anemia pathway downstream of FANCD2 monoubiquitination (designated FANCU) (PMID:27208205), restrains replication fork progression during dNTP imbalance through ATR-mediated phosphorylation at Ser247 (PMID:30566856), and is essential for mammalian meiotic recombination (PMID:30042186). Biallelic XRCC2 mutation causes a Fanconi anemia phenotype (PMID:27208205), and a homozygous p.Leu14Pro mutation causes meiotic arrest and infertility in humans (PMID:30042186). At the organismal level, Xrcc2 loss produces p53-dependent apoptosis of post-mitotic neurons and embryonic lethality (PMID:11118202, PMID:17116431).

Mechanistic history

Synthesis pass · year-by-year structured walk · 23 steps
  1. 1998 High

    Established XRCC2 as a recombinational repair factor by showing human XRCC2 complements the cross-linker sensitivity and instability of mutant cells, placing it in the RecA/RAD51 family.

    Evidence Functional complementation of hamster irs1 cells with human XRCC2 cDNA plus sequence alignment

    PMID:9628903 PMID:9660962

    Open questions at the time
    • Did not define the molecular activity of XRCC2
    • Direct RAD51 interaction shown for XRCC3 but only inferred for XRCC2
  2. 1999 High

    Pinpointed XRCC2's specific pathway role by demonstrating it is required for DSB-induced HR but dispensable for NHEJ.

    Evidence HR and NHEJ reporter assays with transient complementation in XRCC2-deficient hamster cells

    PMID:10517641

    Open questions at the time
    • Mechanism of action within HR not resolved
    • No biochemical activity assigned
  3. 2000 High

    Linked XRCC2 loss to mitotic genome instability and to organismal requirement, showing chromosome missegregation/centrosome fragmentation and embryonic lethality with neuronal apoptosis.

    Evidence Cytological analysis of mutant cell lines; Xrcc2 knockout mouse with histology and chromosome aberration assays

    PMID:11025669 PMID:11118202

    Open questions at the time
    • Connection between HR defect and centrosome fragmentation mechanistic detail unresolved
    • Effector pathway driving apoptosis not yet identified
  4. 2000 High

    Provided the first biochemical handle by purifying a direct XRCC2-RAD51D complex with ssDNA-binding and DNA-stimulated ATPase activity.

    Evidence Protein purification, in vitro ATPase and binding assays, Co-IP from human cells

    PMID:10871607

    Open questions at the time
    • Did not establish how this complex acts on RAD51 filaments
    • Higher-order paralog assembly not characterized
  5. 2001 High

    Defined XRCC2's nuclear function as enabling RAD51 focus formation and showed, via P-loop mutants, that this does not require its own ATP binding.

    Evidence GFP localization, RAD51 focus assay, and P-loop site-directed mutagenesis with complementation

    PMID:11301337

    Open questions at the time
    • Why ATP binding is dispensable for XRCC2 but not other paralogs unexplained
    • Recruitment mechanism to damage sites not defined
  6. 2001 High

    Revealed XRCC2 channels recombination intermediates toward templated repair, as its loss switches Ig diversification from gene conversion to hypermutation.

    Evidence DT40 knockout with sequencing of immunoglobulin V gene diversification products

    PMID:11528482

    Open questions at the time
    • Molecular determinant of pathway channeling not identified
  7. 2002 High

    Demonstrated the XRCC2-RAD51D complex possesses intrinsic recombinase-like activity, catalyzing homologous pairing and forming rings and ssDNA filaments.

    Evidence Co-expression/purification in E. coli, in vitro homologous pairing assay, electron microscopy

    PMID:11834724

    Open questions at the time
    • Relationship of this activity to RAD51 filament assembly in vivo not resolved
    • Structure at near-atomic resolution not yet available
  8. 2002 Medium

    Confirmed XRCC2 is non-redundantly required for RAD51 focus formation after IR and MMC despite normal RAD51 protein levels.

    Evidence Immunofluorescence focus assay and Western blot in deficient and complemented cells

    PMID:12488590

    Open questions at the time
    • Did not establish direct loading mechanism
    • Distinction between early and late focus roles unexplained
  9. 2002 Medium

    Identified amino acid 188 as functionally important and characterized the common R188H variant as having only a weak effect on damage sensitivity.

    Evidence Site-directed mutagenesis and cellular damage sensitivity assay

    PMID:12023985

    Open questions at the time
    • Single lab
    • Biochemical basis of residue 188 importance not determined
  10. 2003 High

    Showed XRCC2 acts non-redundantly in HR in vivo and that a tumour-derived allele separates fork-associated from DSB-associated HR sub-pathways.

    Evidence Spectral karyotyping, gene conversion/SCE assays in Xrcc2-/- MEFs; dominant-negative 342delT allele with HR reporters

    PMID:14645207 PMID:14678973

    Open questions at the time
    • Molecular basis distinguishing fork-associated vs DSB HR not defined
    • Dominant-negative result from single lab
  11. 2004 High

    Established the BCDX2 tetramer's substrate preference, showing it binds branched DNA structures and catalyzes strand annealing.

    Evidence Competitive DNA-binding assay with purified BCDX2 across seven substrates; strand-annealing assay

    PMID:15141025

    Open questions at the time
    • Did not show how substrate binding promotes RAD51 loading
    • Subunit architecture not resolved
  12. 2005 Medium

    Dissected fork-repair sub-pathways, showing XRCC2 is required for RAD51 loading after HU but not thymidine arrest.

    Evidence RAD51 focus and chromatin fractionation assays after HU vs thymidine in deficient cells

    PMID:15861395

    Open questions at the time
    • Identity of XRCC2-independent fork pathway unknown
  13. 2006 High

    Placed p53 but not ATM as the effector of the lethal embryonic response to HR loss, and characterized R188H as conferring relative cisplatin resistance.

    Evidence Xrcc2;Trp53 and Xrcc2;Atm double-knockout mice; DT40 complementation with R188H variant

    PMID:17116431 PMID:17141189

    Open questions at the time
    • p53-activating signal upstream of apoptosis not defined
    • p53 loss could not rescue lethality
  14. 2008 High

    Distinguished XRCC2-dependent DSB repair from XRCC2-independent fork/transcription-associated recombination and showed HR via XRCC2 specifically protects against alkylation lesions.

    Evidence TAR and I-SceI reporter assays; isogenic comparison of HR vs NHEJ mutants with MGMT control and gammaH2AX readouts

    PMID:18840549 PMID:19043071

    Open questions at the time
    • Mechanistic separation of XRCC2-dependent and -independent fork recombination unresolved
  15. 2009 High

    Showed XRCC2 suppresses long-tract gene conversion in an ATP-independent manner, contrasting with the ATP-dependent role of XRCC3.

    Evidence Sister chromatid recombination reporter with wild-type and ATP-binding/hydrolysis mutant XRCC2

    PMID:19470754

    Open questions at the time
    • How XRCC2 controls conversion tract length mechanistically not defined
  16. 2010 Medium

    Confirmed XRCC2 colocalizes with RAD51 at damage sites and interacts with RAD51 and RAD51D, while being important but not strictly essential for RAD51 accumulation.

    Evidence Laser micro-irradiation, yeast two-hybrid, and truncation-mutant complementation

    PMID:20189471

    Open questions at the time
    • Direct vs paralog-mediated RAD51 contact not distinguished
    • Y2H interactions not reconstituted biochemically
  17. 2015 Medium

    Identified transcriptional control of XRCC2 by ZNF281 and showed its silencing impairs DNA repair, while c-Myc binds but does not activate the promoter.

    Evidence ChIP, luciferase reporter, comet assay, and siRNA knockdown

    PMID:26300006

    Open questions at the time
    • Conditions governing ZNF281 vs c-Myc promoter activity unresolved
  18. 2016 High

    Classified XRCC2 as Fanconi anemia gene FANCU acting late, downstream of normal FANCD2 monoubiquitination, via patient-cell complementation.

    Evidence Complementation of patient cells (p.R215X) with MMC sensitivity, chromosome breakage, FANCD2 ubiquitination, and protein stability assays

    PMID:27208205

    Open questions at the time
    • Step in FA pathway between FANCD2 and XRCC2 action not defined
  19. 2018 High

    Uncovered an HDR-independent role: XRCC2/RAD51D restrain fork progression during dNTP imbalance, regulated by ATR phosphorylation at Ser247, and established XRCC2 as essential for meiotic HR.

    Evidence DNA fiber assays, nucleotide pool measurement, S247 phospho-mutant, ATR inhibition; human exome plus knockin mouse with meiotic phenotypes

    PMID:30042186 PMID:30566856

    Open questions at the time
    • How XRCC2 limits RRM2/nucleotide pools mechanistically unresolved
    • Link between fork-restraint function and HR function unclear
  20. 2019 High

    Demonstrated the RAD51D-XRCC2 interaction is functionally required for HR using cancer-associated RAD51D mutations that disrupt binding and abolish DSB repair.

    Evidence Yeast two/three-hybrid, Co-IP in U2OS, and sister chromatid recombination reporter in RAD51D-knockout cells

    PMID:30836272

    Open questions at the time
    • Structural basis of the interface not yet resolved at this stage
  21. 2023 High

    Resolved how BCDX2 acts on RAD51 filaments, showing RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers and stimulates filament nucleation and extension via coupled RAD51B/RAD51C ATPase.

    Evidence Cryo-EM, AlphaFold2 modelling, single-molecule and ATPase assays

    PMID:37344587

    Open questions at the time
    • Dynamics of RAD51B subunit not fully captured
    • How filament loading integrates with fork protection unaddressed
  22. 2026 High

    Distinguished two paralog complexes structurally, showing BCDX2 promotes dynamic filament assembly while the XRCC3 complex caps 5' filament termini for homologous pairing.

    Evidence Cryo-EM with in vitro filament assembly and capping assays

    PMID:41196948

    Open questions at the time
    • Coordination between the two complexes in vivo not defined
    • Regulation of complex switching unknown
  23. 2024 Medium

    Connected XRCC2 to cancer cell proliferation, identifying a c-Myc-XRCC2 transcriptional axis acting through FOS downregulation in NSCLC.

    Evidence ChIP, luciferase reporter, RNA-seq with rescue, shRNA knockdown, and xenografts

    PMID:39153434

    Open questions at the time
    • Single lab
    • Mechanism linking XRCC2 to FOS regulation not defined
    • c-Myc activation contrasts with earlier negative promoter result

Open questions

Synthesis pass · forward-looking unresolved questions
  • How XRCC2's distinct functions—filament-assembly within BCDX2, filament capping within the XRCC3 complex, ATR-regulated fork restraint, and FA-pathway action—are coordinated and switched in vivo remains unresolved.
  • No model integrating the two structurally distinct complexes with the fork-restraint function
  • Upstream regulation of complex choice unknown
  • Role of Ser247 phosphorylation in complex assembly undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 2 GO:0140096 catalytic activity, acting on a protein 2 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 2
Pathway
R-HSA-73894 DNA Repair 3 R-HSA-69306 DNA Replication 2 R-HSA-1474165 Reproduction 1 R-HSA-1640170 Cell Cycle 1
Partners
RAD51RAD51BRAD51CRAD51DXRCC3
Complex memberships
BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2)XRCC3-RAD51C-RAD51D-XRCC2 complex

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 XRCC2 is a member of the RecA/RAD51 family of recombination-repair proteins; the human XRCC2 cDNA complements the DNA cross-linking agent sensitivity and genetic instability of the hamster irs1 mutant cell line, establishing its role in recombinational repair. Functional complementation of mutant hamster cell line (irs1) with human XRCC2 cDNA; sequence alignment Nucleic acids research High 9628903 9660962
1998 XRCC3, but not XRCC2, was shown to interact directly with HsRAD51 by direct interaction assay; XRCC2 and XRCC3 are RAD51-related proteins promoting chromosome stability and protecting against DNA cross-links. Sequence homology analysis; functional complementation; direct interaction assay for XRCC3-RAD51 (not for XRCC2) Molecular cell Medium 9660962
1999 XRCC2 is essential for efficient repair of DNA double-strand breaks by homologous recombination between sister chromatids; XRCC2-deficient hamster cells show >100-fold decrease in HR induced by DSBs, while NHEJ remains normal, and this defect is rescued by transient XRCC2 expression. HR reporter assay in XRCC2-deficient (irs1) hamster cells; transient transfection complementation; NHEJ assay Nature High 10517641
2000 XRCC2 deficiency leads to significant increases in chromosome missegregation and centrosome fragmentation during mitosis, not due to loss of the spindle checkpoint, but linked to unresolved DNA damage. Cytological analysis of chromosome segregation in XRCC2/XRCC3-deficient cell lines; spindle checkpoint assay Nature cell biology High 11025669
2000 Xrcc2 knockout in mice causes embryonic lethality from mid-gestation, with high-frequency apoptotic death of post-mitotic neurons in the developing brain and chromosomal aberrations in embryonic cells, demonstrating a role for homologous recombination in endogenous damage repair during development. Mouse knockout (Xrcc2−/−); histological analysis; chromosomal aberration assay; gamma-ray sensitivity test The EMBO journal High 11118202
2000 RAD51L3 (RAD51D) possesses single-stranded DNA binding activity and DNA-stimulated ATPase activity, and forms a direct protein complex with XRCC2 in human cells, as demonstrated with purified proteins. Protein purification; in vitro ATPase assay; direct binding assay with purified proteins; Co-immunoprecipitation from human cells The Journal of biological chemistry High 10871607
2001 Ablation of XRCC2 in chicken DT40 B cells shifts immunoglobulin V gene diversification from gene conversion (templated) to somatic hypermutation (non-templated), demonstrating XRCC2's role in channeling recombination intermediates toward template-dependent repair. Gene knockout in DT40 cells; sequencing of immunoglobulin V gene diversification products Nature High 11528482
2001 XRCC2 localizes to the nucleus (as a GFP fusion), and is required for damage-dependent RAD51 focus formation; XRCC2 mutants with inactivated ATP-binding P-loop motifs still complement XRCC2-deficient irs1 cells, indicating XRCC2 promotes RAD51-dependent recombination repair without requiring ATP binding. GFP fusion localization; complementation assay; site-directed mutagenesis of P-loop residues; RAD51 focus formation assay The Journal of biological chemistry High 11301337
2002 The purified XRCC2·RAD51D (Xrcc2·Rad51D) complex catalyzes homologous pairing between ssDNA and dsDNA in vitro, forms multimeric ring structures in the absence of DNA, and forms filamentous structures on ssDNA, similar to RAD51, RAD52, and XRCC3·RAD51C. Protein co-expression and purification in E. coli; in vitro homologous pairing assay; electron microscopy The Journal of biological chemistry High 11834724
2002 XRCC2 is required for the formation of RAD51 foci after both ionizing radiation and mitomycin C treatment; irs1 cells lacking XRCC2 fail to form early (type 1) and late (type 2) RAD51 foci despite normal RAD51 protein levels, and XRCC2 complementation restores focus formation. Immunofluorescence RAD51 focus formation assay in XRCC2-deficient (irs1) cells and XRCC2-complemented cells; Western blot for RAD51 levels Journal of biomedicine & biotechnology Medium 12488590
2002 Non-conservative substitution or deletion of amino acid 188 of XRCC2 significantly affects cellular sensitivity to DNA damage; the R188H polymorphic variant (present in 6% of chromosomes) has a weak effect on damage sensitivity. Site-directed mutagenesis of XRCC2 amino acid 188; cellular DNA damage sensitivity assay Human molecular genetics Medium 12023985
2003 Xrcc2−/− mouse embryonic fibroblasts exhibit order-of-magnitude higher chromosomal alterations including aneuploidy and complex exchanges, a 30-fold reduction in gene conversion, and reduced RAD51 focus formation and SCE; these phenotypes resemble Brca disruptions and confirm XRCC2 as a non-redundant HR component. Spectral karyotyping; gene conversion reporter assay; RAD51 focus formation; SCE assay in Xrcc2−/− MEFs Cancer research High 14678973
2003 A tumour-derived XRCC2 mutant allele (342delT) dominantly suppresses HR at stalled replication forks but not at two-ended DSBs, suggesting that XRCC2 participates in at least two mechanistically distinguishable sub-pathways of HR: replication fork-associated and DSB-associated. Expression of dominant-negative XRCC2 mutant in HR-proficient cells with recombination reporter; sensitivity to thymidine and mitomycin C Human molecular genetics Medium 14645207
2004 The BCDX2 complex (RAD51B-RAD51C-RAD51D-XRCC2) preferentially binds branched DNA structures (Y-shaped DNA and Holliday junctions) over linear or nicked duplexes, and catalyzes strand-annealing between long complementary ssDNA molecules. Competitive DNA-binding assay with purified BCDX2 complex using seven DNA substrates; strand-annealing assay Nucleic acids research High 15141025
2005 XRCC2 is required for RAD51 focus formation and chromatin association after hydroxyurea (HU)-induced replication arrest, but not after thymidine-induced arrest, indicating at least two XRCC2-dependent and -independent sub-pathways for repair at stalled replication forks. RAD51 focus formation assay; chromatin fractionation assay; HU and thymidine treatment of XRCC2-deficient (irs1) cells Journal of cellular biochemistry Medium 15861395
2006 The naturally occurring R188H polymorphic variant of XRCC2 confers increased resistance to cisplatin-induced DNA damage compared to wild-type XRCC2, as assayed in chicken DT40 XRCC2-knockout cells complemented with human wild-type or R188H cDNAs. Complementation of Xrcc2−/− DT40 cells with wild-type or R188H XRCC2 cDNA; cisplatin and mitomycin C sensitivity assay Biochemical and biophysical research communications Medium 17141189
2006 Excessive apoptosis in Xrcc2−/− embryos is p53-dependent; loss of p53 restores growth capacity to Xrcc2−/− fibroblasts but cannot rescue embryonic lethality. Loss of ATM in an Xrcc2−/− background has little effect, indicating that the embryonic response to HR loss is not mediated through ATM. Double-knockout mice (Xrcc2−/−;Trp53−/− and Xrcc2−/−;Atm−/−); embryonic analysis; cell growth assay; developmental marker expression DNA repair High 17116431
2008 HR (via XRCC2 and BRCA2) but not NHEJ protects against O6-methylguanine-triggered apoptosis, DSBs, and chromosomal aberrations; cells defective in XRCC2 are hypersensitive to temozolomide/MNNG-induced cell death and show persistent γH2AX foci, while NHEJ mutants (Ku80, DNA-PKcs) are not hypersensitive. Comparison of HR and NHEJ mutant cell lines; apoptosis assay; chromosomal aberration analysis; γH2AX foci assay; MGMT transfection control DNA repair High 18840549
2008 Transcription-associated recombination (TAR) depends on BRCA2 but is independent of XRCC2; XRCC2-deficient irs1 cells are also proficient in recombination induced at slowed replication forks, linking TAR mechanistically to fork-associated recombination rather than DSB repair. HR reporter assay for TAR in XRCC2-deficient and XRCC2-complemented cells; I-SceI-induced DSB repair assay Nucleic acids research Medium 19043071
2009 XRCC2 deficiency biases sister chromatid recombination toward long-tract gene conversion (LTGC); this defect is corrected by wild-type XRCC2 and by XRCC2 mutants defective in ATP binding and hydrolysis, whereas XRCC3-mediated suppression of LTGC requires ATP binding/hydrolysis. SCR reporter assay in XRCC2-deficient cells; complementation with wild-type and ATP-binding/hydrolysis mutant XRCC2 Molecular and cellular biology High 19470754
2010 XRCC2 is important but not essential for the accumulation of RAD51 at DNA damage sites; XRCC2 colocalizes with RAD51 at damage sites; protein truncations of XRCC2 destroy its function; XRCC2 and RAD51L3 (RAD51D) interact with RAD51 in yeast two-hybrid assay. Laser micro-irradiation and immunofluorescence (specialized irradiation for co-localization); yeast two-hybrid; truncation mutagenesis with complementation assay DNA repair Medium 20189471
2015 ZNF281 transcriptionally activates XRCC2 expression through direct DNA binding to its promoter; ZNF281 silencing delays DNA repair after etoposide treatment; c-Myc binds the XRCC2 promoter but cannot activate its transcription or modify ZNF281 activity. Luciferase reporter assay; ChIP (chromatin immunoprecipitation); comet assay; siRNA knockdown Oncogene Medium 26300006
2016 XRCC2 is a Fanconi anemia gene (FANCU); wild-type XRCC2 corrects increased MMC sensitivity, chromosome breakage, and G2-M accumulation in FA patient cells with biallelic XRCC2 mutation; XRCC2 acts late in the FA-BRCA pathway (downstream of FANCD2 monoubiquitination, which is normal in XRCC2-deficient cells); the patient's XRCC2 p.R215X mutant is unstable and reduces levels of other BCDX2 complex proteins. Genetic complementation with wild-type XRCC2 cDNA; MMC sensitivity assay; chromosome breakage assay; cell cycle analysis; FANCD2 monoubiquitination assay; RAD51 focus formation assay; Western blot Journal of medical genetics High 27208205
2018 XRCC2 (FANCU) and its binding partner RAD51D restrain active DNA synthesis during dNTP alterations independently of HDR; XRCC2 absence is associated with elevated RRM2 levels and high nucleotide pools, causing unrestrained fork progression and DNA damage accumulation; this function is regulated by ATR-mediated phosphorylation of XRCC2 at Ser247. DNA fiber assay; RRM2 Western blot; nucleotide pool measurement; ATR inhibition; XRCC2-S247 phosphorylation site mutation Cell reports High 30566856
2018 A homozygous XRCC2 missense mutation (c.41T>C/p.Leu14Pro) causes meiotic arrest, azoospermia, and infertility in humans; knockin mice with the equivalent mutation survive but exhibit meiotic arrest, azoospermia, premature ovarian failure, and infertility, establishing XRCC2 as essential for mammalian meiotic HR. Whole-exome sequencing; CRISPR/Cas9 knockin mouse model; histological and fertility analysis Journal of medical genetics High 30042186
2019 RAD51D cancer-associated mutations G96C and G107V (near/within the Walker A motif) disrupt RAD51D interaction with XRCC2 in yeast two-hybrid and Co-IP, and abolish DSB repair in a sister chromatid recombination reporter, demonstrating that the RAD51D–XRCC2 interaction is required for homologous recombination. Yeast two-hybrid; yeast three-hybrid; Co-immunoprecipitation in U2OS cells; sister chromatid recombination reporter assay in RAD51D knockout cells DNA repair High 30836272
2023 Cryo-EM and AlphaFold2 structural analysis of the BCDX2 complex reveals that RAD51C-RAD51D-XRCC2 mimics three RAD51 protomers aligned within a nucleoprotein filament while RAD51B is highly dynamic; biochemical and single-molecule assays show BCDX2 stimulates nucleation and extension of RAD51 filaments on ssDNA in reactions dependent on coupled ATPase activities of RAD51B and RAD51C. Cryo-electron microscopy; AlphaFold2 modelling; structural proteomics; in vitro RAD51 filament assembly assay; single-molecule analysis; ATPase assay Nature High 37344587
2026 Cryo-EM reveals two distinct heterotetrameric RAD51 paralog complexes: the RAD51B complex (RAD51B-RAD51C-RAD51D-XRCC2) promotes dynamic ATP hydrolysis-dependent RAD51 filament assembly, while the XRCC3 complex (XRCC3-RAD51C-RAD51D-XRCC2) stably caps the 5' termini of RAD51 filaments to promote homologous pairing. Cryo-electron microscopy; in vitro RAD51 filament assembly and capping assays Science (New York, N.Y.) High 41196948
2024 c-Myc acts as a transcriptional activator of XRCC2 in NSCLC, as shown by ChIP and luciferase reporter assays; XRCC2 augments NSCLC cell proliferation through down-regulation of FOS expression; XRCC2 knockdown impairs proliferation in vitro and in vivo. ChIP assay; luciferase reporter assay; RNA sequencing; flow cytometry rescue assay; shRNA knockdown; xenograft mouse model Biomedicine & pharmacotherapy Medium 39153434

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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
1999 Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination. Nature 291 10517641
2000 Mammalian recombination-repair genes XRCC2 and XRCC3 promote correct chromosome segregation. Nature cell biology 196 11025669
2000 Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice. The EMBO journal 194 11118202
2001 Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation. Nature 186 11528482
2012 Rare mutations in XRCC2 increase the risk of breast cancer. American journal of human genetics 138 22464251
1998 The XRCC2 DNA repair gene from human and mouse encodes a novel member of the recA/RAD51 family. Nucleic acids research 132 9628903
2008 Combinational polymorphisms of four DNA repair genes XRCC1, XRCC2, XRCC3, and XRCC4 and their association with oral cancer in Taiwan. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 109 18410587
1999 The XRCC2 and XRCC3 repair genes are required for chromosome stability in mammalian cells. Mutation research 107 10422536
2002 A potential role for the XRCC2 R188H polymorphic site in DNA-damage repair and breast cancer. Human molecular genetics 102 12023985
2000 The RAD51 family member, RAD51L3, is a DNA-stimulated ATPase that forms a complex with XRCC2. The Journal of biological chemistry 92 10871607
2008 Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations by a process leading to SCEs. DNA repair 90 18840549
2000 Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants. Oncogene 90 11126366
2001 XRCC2 is a nuclear RAD51-like protein required for damage-dependent RAD51 focus formation without the need for ATP binding. The Journal of biological chemistry 85 11301337
2009 Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51. Cancer epidemiology 81 20004634
2004 DNA repair gene XRCC2 and XRCC3 polymorphisms and susceptibility to cancers of the upper aerodigestive tract. International journal of cancer 79 15386379
2003 Homologous recombination deficiency leads to profound genetic instability in cells derived from Xrcc2-knockout mice. Cancer research 78 14678973
2008 Genetic polymorphisms in the DNA repair genes XRCC1, XRCC2 and XRCC3 and risk of breast cancer in Cyprus. Breast cancer research and treatment 77 18188695
2017 Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks. Journal of medical genetics 76 28779002
2010 Polymorphisms in RAD51, XRCC2 and XRCC3 genes of the homologous recombination repair in colorectal cancer--a case control study. Molecular biology reports 76 21104022
2016 Complementation of hypersensitivity to DNA interstrand crosslinking agents demonstrates that XRCC2 is a Fanconi anaemia gene. Journal of medical genetics 73 27208205
2004 Preferential binding to branched DNA strands and strand-annealing activity of the human Rad51B, Rad51C, Rad51D and Xrcc2 protein complex. Nucleic acids research 72 15141025
2014 miR-7 inhibits colorectal cancer cell proliferation and induces apoptosis by targeting XRCC2. OncoTargets and therapy 68 24570594
2012 Exome sequencing reveals a novel Fanconi group defined by XRCC2 mutation. Journal of medical genetics 68 22232082
2002 Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex. The Journal of biological chemistry 65 11834724
2007 XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. The American journal of gastroenterology 60 17986315
2023 Structure and function of the RAD51B-RAD51C-RAD51D-XRCC2 tumour suppressor. Nature 58 37344587
2018 XRCC2 mutation causes meiotic arrest, azoospermia and infertility. Journal of medical genetics 58 30042186
2010 The importance of XRCC2 in RAD51-related DNA damage repair. DNA repair 54 20189471
1997 The XRCC2 DNA repair gene: identification of a positional candidate. Genomics 52 9126486
2009 XRCC2 and XRCC3 regulate the balance between short- and long-tract gene conversions between sister chromatids. Molecular and cellular biology 50 19470754
2011 A role for XRCC2 gene polymorphisms in breast cancer risk and survival. Journal of medical genetics 48 21632523
1995 Localization to chromosome 7q36.1 of the human XRCC2 gene, determining sensitivity to DNA-damaging agents. Human molecular genetics 48 7711722
2011 Association studies of OGG1, XRCC1, XRCC2 and XRCC3 polymorphisms with differentiated thyroid cancer. Mutation research 46 21414327
2013 Roles of XRCC2, RAD51B and RAD51D in RAD51-independent SSA recombination. PLoS genetics 45 24278037
2015 ZNF281 contributes to the DNA damage response by controlling the expression of XRCC2 and XRCC4. Oncogene 39 26300006
2012 Polymorphism of the DNA repair genes RAD51 and XRCC2 in smoking- and drinking-related laryngeal cancer in a Polish population. Archives of medical science : AMS 39 23319983
2005 Genetic polymorphisms in XRCC1, APE1, ADPRT, XRCC2, and XRCC3 and risk of chronic benzene poisoning in a Chinese occupational population. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 38 16284386
2018 XRCC2 Regulates Replication Fork Progression during dNTP Alterations. Cell reports 37 30566856
2009 Genetic variants in XRCC2: new insights into colorectal cancer tumorigenesis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 37 19690184
2022 PARP inhibitor olaparib enhances the efficacy of radiotherapy on XRCC2-deficient colorectal cancer cells. Cell death & disease 34 35643812
2015 XRCC2 as a predictive biomarker for radioresistance in locally advanced rectal cancer patients undergoing preoperative radiotherapy. Oncotarget 32 26320178
2014 Correlation between selected XRCC2, XRCC3 and RAD51 gene polymorphisms and primary breast cancer in women in Pakistan. Asian Pacific journal of cancer prevention : APJCP 32 25556451
2012 Rare variants in XRCC2 as breast cancer susceptibility alleles. Journal of medical genetics 32 23054243
2006 A naturally occurring genetic variant of human XRCC2 (R188H) confers increased resistance to cisplatin-induced DNA damage. Biochemical and biophysical research communications 32 17141189
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
2010 Genetics polymorphism in DNA repair genes by base excision repair pathway (XRCC1) and homologous recombination (XRCC2 and RAD51) and the risk of breast carcinoma in the Polish population. Polish journal of pathology : official journal of the Polish Society of Pathologists 30 21290343
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
2012 The association between polymorphisms of the RAD51-G135C, XRCC2-Arg188His and XRCC3-Thr241Met genes and clinico-pathologic features in breast cancer in Poland. European journal of gynaecological oncology 28 22611952
2005 Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide. Cancer letters 28 16298473
1995 Assignment of the XRCC2 human DNA repair gene to chromosome 7q36 by complementation analysis. Genomics 28 7607692
2014 Association between single nucleotide polymorphisms (SNPs) of XRCC2 and XRCC3 homologous recombination repair genes and triple-negative breast cancer in Polish women. Clinical and experimental medicine 27 24728564
2012 Single nucleotide polymorphisms of RAD51 G135C, XRCC2 Arg188His and XRCC3 Thr241Met homologous recombination repair genes and the risk of sporadic endometrial cancer in Polish women. The journal of obstetrics and gynaecology research 26 22487057
2014 XRCC2 promotes colorectal cancer cell growth, regulates cell cycle progression, and apoptosis. Medicine 25 25526472
2021 XRCC2 repairs mitochondrial DNA damage and fuels malignant behavior in hepatocellular carcinoma. Cancer letters 24 33964350
2015 Polymorphisms of homologous recombination RAD51, RAD51B, XRCC2, and XRCC3 genes and the risk of prostate cancer. Analytical cellular pathology (Amsterdam) 24 26339569
2014 Combined effect of tobacco and DNA repair genes polymorphisms of XRCC1 and XRCC2 influence high risk of head and neck squamous cell carcinoma in northeast Indian population. Medical oncology (Northwood, London, England) 24 24958516
2013 XRCC2 R188H (rs3218536), XRCC3 T241M (rs861539) and R243H (rs77381814) single nucleotide polymorphisms in cervical cancer risk. Pathology oncology research : POR 24 23539294
2006 A role for Xrcc2 in the early stages of mouse development. DNA repair 24 17116431
2014 Impact of XRCC2 Arg188His polymorphism on cancer susceptibility: a meta-analysis. PloS one 23 24621646
2010 XRCC2 Arg188His polymorphism is not directly associated with breast cancer risk: evidence from 37,369 subjects. Breast cancer research and treatment 23 20127279
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
2009 The interaction profile of homologous recombination repair proteins RAD51C, RAD51D and XRCC2 as determined by proteomic analysis. Proteomics 21 19658102
2005 Differential roles of XRCC2 in homologous recombinational repair of stalled replication forks. Journal of cellular biochemistry 20 15861395
2019 RAD51D splice variants and cancer-associated mutations reveal XRCC2 interaction to be critical for homologous recombination. DNA repair 19 30836272
2018 6-OHBDE-47 induces transcriptomic alterations of CYP1A1, XRCC2, HSPA1A, EGR1 genes and trigger apoptosis in HepG2 cells. Toxicology 19 29601929
2008 Transcription-associated recombination is independent of XRCC2 and mechanistically separate from homology-directed DNA double-strand break repair. Nucleic acids research 19 19043071
2015 Single Nucleotide Polymorphisms (SNPs) of RAD51-G172T and XRCC2-41657C/T Homologous Recombination Repair Genes and the Risk of Triple- Negative Breast Cancer in Polish Women. Pathology oncology research : POR 16 25743260
2003 A tumour-derived mutant allele of XRCC2 preferentially suppresses homologous recombination at DNA replication forks. Human molecular genetics 16 14645207
2019 XRCC2 (X-ray repair cross complementing 2). Atlas of genetics and cytogenetics in oncology and haematology 14 31275435
2019 Inherited variants in XRCC2 and the risk of breast cancer. Breast cancer research and treatment 14 31463769
2018 Use of the XRCC2 promoter for in vivo cancer diagnosis and therapy. Cell death & disease 14 29549248
2013 Hypermethylation of RAD51L3 and XRCC2 genes to predict late toxicity in chemoradiotherapy-treated cervical cancer patients. Folia biologica 14 24485306
2005 Defective DNA mismatch repair and XRCC2 mutation in uterine carcinosarcomas. Gynecologic oncology 14 16169065
2002 XRCC2 is Required for the Formation of Rad51 Foci Induced by Ionizing Radiation and DNA Cross-Linking Agent Mitomycin C. Journal of biomedicine & biotechnology 14 12488590
2020 Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk. Clinical and experimental gastroenterology 13 32214837
2020 ERCC2 Lys751Gln rs13181 and XRCC2 Arg188His rs3218536 Gene Polymorphisms Contribute to Subsceptibility of Colon, Gastric, HCC, Lung And Prostate Cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 13 32277685
2017 XRCC2-Deficient Cells are Highly Sensitive to 5-Fluorouracil in Colorectal Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 13 28977800
2014 The Arg188His polymorphism in the XRCC2 gene and the risk of cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 24414483
2016 Polymorphisms of XRCC1 and XRCC2 DNA Repair genes and Interaction with Environmental Factors Influence the Risk of Nasopharyngeal Carcinoma in Northeast India. Asian Pacific journal of cancer prevention : APJCP 12 27356695
2016 MiRNA-binding site functional polymorphisms in DNA repair genes RAD51, RAD52, and XRCC2 and breast cancer risk in Chinese population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 27726100
2014 Polymorphisms in DNA repair genes XRCC2 and XRCC3 risk of gastric cancer in Turkey. Bosnian journal of basic medical sciences 12 25428673
2021 A PRISMA-compliant meta-analysis on association between X-ray repair cross complementing (XRCC1, XRCC2, and XRCC3) polymorphisms and oral cancer susceptibility. Gene 11 33631241
2021 Association of RAD51 and XRCC2 Gene Polymorphisms with Cervical Cancer Risk in the Bangladeshi Women. Asian Pacific journal of cancer prevention : APJCP 11 34319032
2016 Functional Analysis of Missense Variants in the Putative Breast Cancer Susceptibility Gene XRCC2. Human mutation 11 27233470
2014 shRNA-mediated XRCC2 gene knockdown efficiently sensitizes colon tumor cells to X-ray irradiation in vitro and in vivo. International journal of molecular sciences 11 24481064
2014 XRCC2 rs3218536 polymorphism decreases the sensitivity of colorectal cancer cells to poly(ADP-ribose) polymerase 1 inhibitor. Oncology letters 11 25120693
2014 Association of reduced XRCC2 expression with lymph node metastasis in breast cancer tissues. Familial cancer 11 25159888
2010 Xrcc2 modulates spontaneous and radiation-induced tumorigenesis in Apcmin/+ mice. Molecular cancer research : MCR 11 20671066
2021 Association between RAD51, XRCC2 and XRCC3 gene polymorphisms and risk of ovarian cancer: a case control and an in silico study. Molecular biology reports 10 34097201
2017 Haplotype analysis of XRCC2 gene polymorphisms and association with increased risk of head and neck cancer. Scientific reports 10 29038438
2022 Homologous recombination DNA repair gene RAD51, XRCC2 & XRCC3 polymorphisms and breast cancer risk in South Indian women. PloS one 9 35061678
2015 The effect of polymorphism in DNA repair genes RAD51 and XRCC2 in colorectal cancer in Turkish population. International journal of clinical and experimental medicine 8 25932214
2015 Arg188His polymorphism in the XRCC2 gene and the risk of ovarian cancer: a meta-analysis. Genetics and molecular research : GMR 8 26400309
2013 Common gene variants in RAD51, XRCC2 and XPD are not associated with clinical outcome in soft-tissue sarcoma patients. Cancer epidemiology 8 24189466
2001 The XRCC2 human repair gene influences recombinational rearrangements leading to chromatid breaks. International journal of radiation biology 8 11571019
2026 Cryo-electron microscopic visualization of RAD51 filament assembly and end-capping by XRCC3-RAD51C-RAD51D-XRCC2. Science (New York, N.Y.) 7 41196948
2024 c-Myc-XRCC2-FOS axis promotes the proliferation and the resistance to Doxorubicin of NSCLC. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 7 39153434
2015 Analysis of XRCC2 and XRCC3 gene polymorphisms in pancreatic cancer. Biomedical reports 7 26893845

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