Affinage

Showing XRCC5 — KU80 is a alias.

XRCC5

DNA repair protein Ku80 · UniProt P13010

Length
732 aa
Mass
82.7 kDa
Annotated
2026-06-11
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

XRCC5 encodes Ku80 (Ku86), the DNA-binding subunit of the DNA-dependent protein kinase that functions as the central sensor of DNA double-strand breaks (DSBs) and is required for non-homologous end joining (NHEJ), V(D)J recombination, and immunoglobulin class-switch recombination (PMID:8073286, PMID:8700231, PMID:9545251). Ku80 forms an obligate heterodimer with Ku70, and heterodimerization precedes DNA end binding and is required for nuclear localization, Ku70 stabilization, and recruitment to breaks (PMID:8756676, PMID:12518983, PMID:15817152). Loading at DSBs requires the Ku80 N-terminal alpha/beta, DNA-binding, and Ku70-binding domains, while the C-terminal ~178 residues are dispensable for DNA end-binding but mediate recruitment of DNA-PKcs and support DNA-PKcs autophosphorylation at Thr2647 needed for Artemis-dependent end processing and coding-joint formation (PMID:10207052, PMID:18164703, PMID:19103741). Structural and biophysical work defines the Ku80 alpha/beta and von Willebrand antigen (vWA) domains as docking surfaces for the Ku-binding motifs of NHEJ factors APLF, XLF, MRI and WRN, with mutation of these sites impairing NHEJ efficiency, accuracy, and radioresistance (PMID:30291363, PMID:31733588). Ku80 occupancy at breaks is dynamically controlled by post-translational modification: K48-linked polyubiquitylation drives its removal from repaired DNA independent of proteasomal degradation, opposed by the deubiquitylases UCHL3 and OTUD5, and a damage-induced K568 crotonylation-to-SUMOylation switch promotes DNA-PK complex assembly and DNA-PKcs S2056 autophosphorylation (PMID:18678709, PMID:30559450, PMID:30980112, PMID:40254688). Beyond NHEJ, Ku80 acts as a caretaker tumor suppressor that maintains genomic stability, suppresses telomeric fusions and lethal t-circle formation, and is essential in human cells through its telomere-protective role; loss produces chromosomal aberrations, premature aging phenotypes, and, with p53 loss, lymphomagenesis (PMID:10485901, PMID:10761921, PMID:11256607, PMID:11792868, PMID:19581589). Ku80 additionally participates in replication origin firing (PMID:16014376) and functions as a sequence-associated transcriptional regulator at multiple promoters, repressing class-switch regulatory elements and xanthine oxidoreductase while activating COX-2 and PDK1 in cancer contexts (PMID:12672812, PMID:14761964, PMID:25797267, PMID:31023624). The alternatively encoded KARP-1 protein, transcribed from an upstream promoter at the Ku86 locus and induced by ATM/p53-dependent DNA damage signaling, modulates DNA-PK activity (PMID:9214634, PMID:9636207).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1994 High

    Established the molecular identity and core function of XRCC5 by showing it encodes the DNA-binding Ku80 subunit required for DSB repair and V(D)J recombination.

    Evidence Genetic complementation of radiosensitive xrs-6 CHO mutants with human XRCC5 cDNA plus biochemical protein identification

    PMID:8073286

    Open questions at the time
    • Did not resolve the structural basis of DNA end recognition
    • Did not define partner factors recruited downstream
  2. 1996 High

    Defined the in vivo requirement for Ku80 in lymphocyte development and V(D)J recombination, distinguishing its role as acting after DNA cleavage to remodel end-processing intermediates.

    Evidence Targeted Ku80/Ku86 knockout mice with lymphocyte development assays and analysis of V(D)J coding/signal-joint intermediates

    PMID:8700231 PMID:8756720

    Open questions at the time
    • Did not identify the biochemical step Ku80 performs on cleaved ends
    • Did not separate DSB-repair from telomere roles
  3. 1997 High

    Mapped the domains governing heterodimer assembly and DNA end binding, showing heterodimerization precedes DNA binding and correlates with DNA-PK activation.

    Evidence Deletion/point mutagenesis of Ku70 and Ku80 with reconstitution and DNA end-binding/DNA-PK activity assays in CHO and ES cells

    PMID:8756676 PMID:9032253 PMID:9362500

    Open questions at the time
    • Did not show how DNA-PKcs is engaged by the heterodimer
    • Atomic structure not yet available
  4. 1998 Medium

    Identified KARP-1 as an alternative product of the Ku86 locus that modulates DNA-PK activity and is induced through ATM/p53-dependent DNA damage signaling.

    Evidence cDNA cloning, dominant-negative expression, antibody neutralization of DNA-PK, and mRNA induction in ATM- and p53-deficient cells

    PMID:9214634 PMID:9636207

    Open questions at the time
    • Single-lab characterization without independent replication
    • Molecular mechanism of DNA-PK modulation by the leucine zipper not resolved
  5. 1998 High

    Extended Ku80's DSB-repair role to immunoglobulin class-switch recombination, showing it acts after switch-region DSB formation.

    Evidence Ku80-knockout mice with pre-rearranged Ig genes; class-switch assay and switch-region DSB detection

    PMID:9545251 PMID:9826756

    Open questions at the time
    • Did not define the joining factors Ku80 coordinates during switching
  6. 2000 High

    Established Ku80 as a caretaker tumor suppressor and direct telomere protector, separating telomere maintenance from telomere length.

    Evidence Ku80/p53 double-knockout mice with cytogenetics and tumor monitoring; Ku86-null cells with telomere FISH and fusion analysis

    PMID:10485901 PMID:10761921 PMID:11256607

    Open questions at the time
    • Molecular mechanism of telomere fusion suppression not defined
    • Link between premature aging and specific Ku80 activities unresolved
  7. 2002 High

    Demonstrated Ku86 is essential in human cells and limits telomerase access, with essentiality later traced to suppression of lethal t-circle formation rather than NHEJ.

    Evidence AAV-mediated gene targeting in human HCT116 cells; Ku86/mTERC double-knockout mice; conditional null t-circle assays

    PMID:11792868 PMID:11980718 PMID:19581589

    Open questions at the time
    • Mechanism by which Ku86 restrains telomeric recombination not fully resolved
  8. 2002 Medium

    Connected Ku80 to broader genome-stability networks and to DNA replication initiation beyond its DSB-repair role.

    Evidence PARP-1/Ku80 double-knockout mouse genetics; ChIP at replication origins with nascent-strand and cell-cycle analysis in Ku80+/- human cells

    PMID:12460917 PMID:16014376

    Open questions at the time
    • Direct biochemical role of Ku80 at origins not defined
    • Single-lab replication-origin findings
  9. 2004 Medium

    Revealed a sequence-associated transcriptional regulatory function for Ku80 at gene promoters, acting in complexes with homeodomain and E-box factors.

    Evidence ChIP, EMSA, co-IP and reporter assays at Igamma/Iepsilon switch elements and the hXOR promoter

    PMID:12672812 PMID:14761964

    Open questions at the time
    • Whether transcriptional activity is separable from DNA-end-binding undefined
    • Single-lab promoter studies
  10. 2006 Medium

    Provided the first structural view of the full-length heterodimer and showed the Ku80 C-terminal domain undergoes conformational change to recruit DNA-PKcs.

    Evidence Single-particle electron microscopy 3D reconstruction of Ku70-Ku80 with DNA and DNA-PKcs at 25 Å

    PMID:17159921

    Open questions at the time
    • Low resolution limited atomic detail
    • Did not define KBM-docking surfaces
  11. 2008 High

    Defined how Ku80 is cleared from DNA after repair and dissected the C-terminal contribution to DNA-PKcs autophosphorylation and Artemis-dependent end processing.

    Evidence Xenopus egg-extract DSB system with linkage-specific ubiquitin analysis; Ku80 C-terminal deletion cells with site-specific autophosphorylation antibodies and Artemis assays

    PMID:18678709 PMID:19103741

    Open questions at the time
    • E3 ligase identity and recruitment timing not fully defined
    • Relationship between removal and downstream resection unclear
  12. 2018 High

    Established the structural basis for Ku80 as a docking hub, defining alpha/beta and vWA domain pockets that bind APLF, XLF, MRI and WRN KBM motifs to organize NHEJ.

    Evidence X-ray crystallography of Ku-DNA-KBM complexes and isolated vWA domain with KBM peptides; NMR, fluorescence polarization, and NHEJ/radiosensitivity assays

    PMID:30291363 PMID:31733588

    Open questions at the time
    • Conditional accessibility of the X-KBM pocket in vivo not fully resolved
    • Order of factor recruitment to these sites undefined
  13. 2019 Medium

    Identified deubiquitylase control of Ku80 stability and chromatin retention, balancing NHEJ versus homologous recombination through Ku80 deubiquitylation.

    Evidence Co-IP and in vitro DUB assays for UCHL3 and OTUD5 with NHEJ/HR reporters and end-resection assays

    PMID:30559450 PMID:30980112

    Open questions at the time
    • Single-lab studies for each DUB
    • Coordination between ubiquitylation and SUMO/crotonylation switches not integrated
  14. 2025 High

    Uncovered a damage-induced K568 crotonylation-to-SUMOylation conversion that licenses DNA-PK complex assembly and S2056 autophosphorylation, a targetable radiosensitization node.

    Evidence Quantitative crotonylome mass spectrometry, site-directed mutagenesis, co-IP, autophosphorylation assays, and xenograft radiotherapy model

    PMID:40254688

    Open questions at the time
    • Single-lab discovery
    • Interplay with ubiquitylation-driven removal not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How Ku80's diverse non-NHEJ functions — telomere protection, replication origin firing, and promoter-specific transcriptional regulation — are mechanistically coordinated with its core DNA-end-binding activity remains unresolved.
  • No unified model linking DNA-end-binding to transcriptional regulation
  • Telomere-protection mechanism at the molecular level undefined
  • Integration of the full PTM code governing Ku80 occupancy not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3 GO:0005730 nucleolus 1
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 3 R-HSA-69306 DNA Replication 1
Partners
APLFOTUD5PARP1PRKDCUCHL3WRNXLFXRCC6
Complex memberships
DNA-PK complexKu70/Ku80 heterodimer

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 XRCC5 encodes Ku80, the 80 kDa subunit of the Ku protein. Ku80 is the DNA-binding component of the DNA-dependent protein kinase (DNA-PK) and is required for DNA double-strand break repair and V(D)J recombination, as shown by genetic complementation of xrs-6 CHO mutants and biochemical identification of the Ku80 protein. Genetic complementation of radiosensitive xrs-6 CHO mutant cells with human XRCC5 cDNA; biochemical co-purification and protein identification Science High 8073286
1996 Ku80 is the DNA-binding subunit of DNA-PK in vivo; Ku80-deficient mice show arrested T and B lymphocyte development due to defective V(D)J recombination and exhibit a growth defect, demonstrating Ku80's essential role in DNA DSB repair and lymphocyte development. Targeted gene disruption (knockout) in mice; lymphocyte development assay; cell proliferation assay Nature High 8700231
1996 Ku86 is essential for V(D)J recombination coding joint and signal joint formation in vivo. In Ku86-deficient mice, both hairpin coding ends and blunt signal ends accumulate, indicating Ku86 is required after DNA cleavage to remodel or disassemble DNA-protein complexes for further processing and joining. Knockout mouse model; Southern blot and PCR analysis of V(D)J intermediates Cell High 8756720
1996 The C-terminal 20 kDa region of Ku70 and the C-terminal 32 kDa region of Ku86 are required for subunit-subunit interaction to form the heterodimer, and heterodimer assembly precedes DNA end binding. The C-terminal 45 kDa of Ku86 is required for DNA end binding activity. Deletion mutagenesis of Ku70 and Ku86; biochemical reconstitution of heterodimer; DNA end-binding assays Molecular and cellular biology High 8756676
1997 xrs mutants defective in Ku80 lack double-stranded DNA end-binding and DNA-PK activities, and have low or undetectable Ku70 and Ku80 protein. Site-directed mutagenesis showed that previously proposed ATP-binding and phosphorylation sites are not required for Ku80 activity, whereas N-terminal deletions of more than 7 amino acids cause severe loss of activities. Molecular characterization of CHO mutant cell lines; site-directed mutagenesis; DNA end-binding assay; DNA-PK activity assay Molecular and cellular biology High 9032253
1997 Ku70 requires heterodimerization with Ku80 and DNA binding for double-strand break repair. A core region of Ku70 is responsible for DNA end binding and heterodimerization, which correlates with DNA-PK activation, although the roles in DNA-PK activation and IR repair can be separated by specific mutations. Knockout ES cell complementation; truncation and chimeric Ku70 mutants; DNA end binding assay; DNA-PK activity assay; IR survival assay The EMBO journal High 9362500
1997 A second gene, KARP-1, is expressed from the Ku86 locus using an upstream promoter and additional exons, encoding a protein with a leucine zipper domain appended to the Ku86 sequence. KARP-1 acts as a regulator of DNA-PK activity; dominant-negative KARP-1 constructs diminish DNA-PK activity and cause X-ray hypersensitivity, and KARP-1 antibody neutralizes DNA-PK activity in vitro. cDNA cloning; stable cell line expression of dominant-negative constructs; DNA-PK activity assay; antibody neutralization in vitro The EMBO journal Medium 9214634
1998 KARP-1 expression is significantly upregulated after DNA damage in a manner completely dependent on the ATM and p53 gene products, consistent with a p53 binding site in the second intron of the KARP-1 locus, linking ATM, p53, and KARP-1 in a DNA damage response pathway. mRNA induction assay; analysis in ATM-deficient and p53-deficient cell lines; promoter analysis Proceedings of the National Academy of Sciences of the United States of America Medium 9636207
1998 Ku80 is required for immunoglobulin isotype switch recombination in vivo. Ku80-deficient B cells form switch region-specific DSBs but fail to complete switch recombination, demonstrating Ku80 functions in DSB repair during class switching. Ku80 knockout mouse with pre-rearranged Ig genes to rescue B-cell development; Ig class switch assay; detection of switch-region DSBs The EMBO journal High 9545251
1998 In cells lacking Ku86 or XRCC4, joining of both matched and mismatched DNA ends occurs efficiently, but junctions show a strong preference for microhomology-containing sequences, indicating that in the absence of Ku86, base-pairing interactions assist end joining, suggesting Ku86 normally participates in aligning or stabilizing repair intermediates. In vivo plasmid end-joining assay; junction sequence analysis in Ku86- and XRCC4-deficient cells Nucleic acids research Medium 9826756
1999 The C-terminal 178 amino acids of Ku80 are dispensable for DNA end-binding but are required for efficient interaction with DNA-PKcs and for DNA-PK activity. Cells expressing C-terminally truncated Ku80 are radiation-sensitive and can form signal joints but not coding joints during V(D)J recombination, phenocopying SCID cells. A point mutation in the Ku70-Ku80 interaction domain in xrs-2 cells abrogates heterodimerization and DNA end-binding. 3' deletion analysis of Ku80; cell-based V(D)J recombination assay; DNA-PK activity assay; radiation sensitivity assay; point mutagenesis Molecular and cellular biology High 10207052
1999 Ku86-deficient mice exhibit premature senescence-associated phenotypes including osteopenia, atrophic skin, hepatocellular degeneration, and early mortality, indicating that Ku86-dependent chromosomal metabolism is important for the onset of age-specific changes. Ku86 knockout mouse histopathological analysis; survival analysis Proceedings of the National Academy of Sciences of the United States of America Medium 10485901
2000 Ku80-deficient mouse cells display marked chromosomal aberrations including breakage, translocations, and aneuploidy. Loss of Ku80 combined with p53 loss promotes disseminated pro-B-cell lymphoma involving IgH/c-Myc translocations, establishing Ku80 as a caretaker tumor suppressor that maintains genomic stability by suppressing chromosomal rearrangements. Ku80/p53 double-knockout mice; cytogenetic analysis; tumor incidence monitoring Nature High 10761921
2000 Mammalian Ku86 prevents telomeric fusions independently of telomere length and G-strand overhang integrity; Ku86-deficient mouse cells show telomeric fusions despite having long telomeres, demonstrating a direct protective role for Ku86 at telomeres. Ku86 knockout mouse cells; telomere length measurement by FISH; analysis of chromosomal fusions EMBO reports High 11256607
2002 Ku86 is essential in human somatic cells. Heterozygous disruption causes haploinsufficiency with increased polyploidy, reduced proliferation, and elevated p53. Complete functional inactivation leads to a drastically reduced doubling time followed by apoptosis after limited cell divisions. Gene targeting (AAV-mediated) in human HCT116 cells; clonogenic assay; flow cytometry; Western blot Proceedings of the National Academy of Sciences of the United States of America High 11792868
2002 Ku86 mediates chromosomal fusions triggered by critically short telomeres in telomerase-deficient mice. Absence of Ku86 prevents end-to-end chromosomal fusions and rescues germ cell apoptosis in telomerase-deficient mice. In telomerase-proficient cells, Ku86 deficiency results in telomerase-dependent telomere elongation, suggesting Ku86 limits telomerase access to normal-length telomeres. Double-knockout mice (Ku86-/-/mTERC-/-); cytogenetic analysis; telomere length measurement The EMBO journal High 11980718
2002 Ku80 nuclear localization requires heterodimerization; Ku70 alone cannot accumulate at DSBs but does so when bound to Ku80. N-terminal deletion of Ku80 abolishes its accumulation at DSBs even when Ku70-binding is retained, identifying the N-terminal alpha/beta, DNA-binding, and Ku70-binding domains as required for DSB recognition. Live cell imaging of EGFP-Ku80 after laser microirradiation; deletion and point mutant analysis Journal of radiation research Medium 12518983
2002 PARP-1 and Ku80 interact functionally; PARP-1/Ku80 double null mice die at embryonic day 9.5, and haplo-insufficiency of Ku80 in PARP-1-deficient mice promotes hepatocellular carcinoma with elevated chromosomal instability, demonstrating synergistic roles in DNA end processing and genomic stability. Double-knockout mouse model; cytogenetic analysis; histopathology Cancer research High 12460917
2003 The Ku70/Ku86 heterodimer binds as a complex with HoxC4 and Oct-1 homeodomain proteins to ATTT switch regulatory elements in the Igamma and Iepsilon promoters to repress class switch recombination to IgG and IgE. CD40 signaling dissociates this complex, relieving transcriptional repression and permitting CSR. Chromatin immunoprecipitation; electrophoretic mobility shift assay; co-immunoprecipitation; luciferase reporter assay The Journal of biological chemistry Medium 12672812
2004 The Ku70-binding site of Ku80 is required for stabilization of Ku70 in the cytoplasm and for nuclear translocation of Ku80 via heterodimerization with Ku70. Nuclear translocation through this site as well as through Ku80's NLS contribute to Ku80-dependent DNA repair. Stable cell lines expressing EGFP-tagged Ku80 wild-type and mutants in Ku80-deficient cells; fluorescence microscopy; DNA repair assay Experimental cell research Medium 15817152
2004 Ku86 is required for normal non-homologous end joining. Ku86-deficient cells show greatly reduced NHEJ efficiency, increased use of microhomologies at junctions, and higher frequency of DNA insertions. DNA-PKcs deficiency does not impair NHEJ efficiency in this assay. Transient transfection assay with linearized plasmid; junction sequence analysis in Ku86- and DNA-PKcs-deficient cell lines Mutation research Medium 15450431
2004 Ku86 binds to the Ku86 site adjacent to E-box elements in the human xanthine oxidoreductase (hXOR) promoter. The Ku86/DNA-PK complex interacts with AREB6-like proteins at the E-box to repress basal hXOR transcription. Loss of Ku86 increases hXOR promoter activity. DNA affinity purification; EMSA; co-immunoprecipitation; site-directed mutagenesis; reporter gene assay The Journal of biological chemistry Medium 14761964
2004 Ku70/Ku80 and DNA-PKcs modulate RAG-mediated cleavage during V(D)J recombination by preferentially inhibiting 12/12 and 23/23 cleavage, thereby increasing 12/23 rule specificity. This indicates Ku and DNA-PK are present upstream of DNA cleavage events. Protein fractionation; biochemical cleavage assay with purified components The Journal of biological chemistry Medium 15123719
2005 Ku80 deficiency in haploinsufficient HCT116 Ku80+/- cells reduces binding of Ku80 and Ku70 to chromosomal replication origins (lamin B2, beta-globin, c-myc) and decreases nascent strand DNA abundance at these origins, accompanied by a prolonged G1 phase, demonstrating a role for Ku80 in DNA replication initiation. Western blot; chromatin immunoprecipitation (ChIP) at replication origins; nascent strand abundance assay; cell cycle analysis Journal of cell science Medium 16014376
2006 Structural model of full-length human Ku70-Ku80 heterodimer at 25 Å resolution determined by single-particle electron microscopy. The study maps C-terminal regions of both subunits and their conformational changes upon DNA and DNA-PKcs binding, showing the Ku80 C-terminal domain undergoes conformational change to recruit DNA-PKcs. Single-particle electron microscopy; 3D reconstruction; mapping of C-terminal domains in complex with DNA and DNA-PKcs EMBO reports Medium 17159921
2007 EGFP-Ku80 accumulates at DSBs immediately after irradiation in living cells. Ku70 alone cannot accumulate at DSBs but does so when bound to Ku80. N-terminal deletion of Ku80 abolishes DSB accumulation while retaining Ku70-binding activity, identifying three domains (N-terminal alpha/beta, DNA-binding, and Ku70-binding domains) as necessary for Ku80 accumulation at DSBs. Live cell fluorescence imaging of EGFP-Ku80 fusions after laser microirradiation; deletion mutagenesis Experimental cell research Medium 18164703
2008 Ku80 is removed from DNA after DSB repair through K48-linked polyubiquitylation mediated by the SCF (Skp1-Cul1-F-box) complex in Xenopus egg extract. K48-linked polyubiquitylation is required for efficient removal of Ku80 from DNA but proteasomal degradation is not required. NHEJ completion and Ku80 removal from DNA are independent events. Xenopus egg extract DSB repair system; mass spectrometry identification of ubiquitylated proteins; ubiquitin linkage analysis; proteasome inhibitor experiments The Journal of cell biology High 18678709
2008 The Ku80 carboxy terminus supports DNA-PKcs autophosphorylation at Thr2647 (but not Ser2056), which is required for Artemis nuclease activity and subsequent DNA end processing. The Ku80 C-terminus is not absolutely required for DNA-PKcs recruitment or initial activation at DSBs. Ku80 C-terminal deletion cells; DNA-PK autophosphorylation site-specific antibodies; Artemis nuclease activity assay; ionizing radiation sensitivity assay Molecular and cellular biology High 19103741
2008 Ku70 and Ku80 interact physically with full-length RAG1, providing a biochemical link between the cleavage and joining phases of V(D)J recombination. Co-immunoprecipitation; pulldown assay Nucleic acids research Low 18281312
2009 Ku86 represses lethal telomere deletion events (t-circle formation) in human somatic cells. Conditional loss of Ku86 results in massive telomere loss as t-circles and cell death, demonstrating that Ku86 is essential in human cells due to its role in telomere maintenance rather than NHEJ or V(D)J recombination. Conditional Ku86 null allele via AAV-mediated gene targeting; telomere circle (t-circle) assay; cell viability assay Proceedings of the National Academy of Sciences of the United States of America High 19581589
2012 PMA stimulation induces poly(ADP-ribosyl)ation of Ku86, causing its dissociation from the histamine H1 receptor gene promoter region B1, which is required for promoter activity. Ku86 knockdown enhances H1R gene up-regulation, identifying a repressive transcriptional role for Ku86 at the H1R promoter via PKCδ/ERK/PARP-1 signaling. Luciferase reporter assay; EMSA; chromatin immunoprecipitation; siRNA knockdown; pharmacological inhibitors Scientific reports Medium 23209876
2015 Ku80 promotes COX-2 expression by binding to the COX-2 gene promoter and cooperating with CBP. CBP acetylates Ku80, and overexpression of CBP (but not its HAT-domain deletion mutant) increases Ku80 acetylation, thereby promoting COX-2 expression and lung cancer cell growth. Streptavidin-agarose pulldown; proteomics; co-immunoprecipitation; siRNA knockdown; reporter assay; xenograft mouse model Oncotarget Medium 25797267
2016 EAF2 is required for the recruitment and retention of Ku70/Ku80 at DNA damage sites. EAF2 knockdown sensitizes prostate cancer cells to DNA damage and abolishes androgen-mediated repression of DNA damage (γH2AX), placing EAF2 upstream of Ku70/Ku80 in NHEJ. siRNA knockdown; laser microirradiation and foci assay; γH2AX immunofluorescence; Ku70/Ku80 chromatin recruitment assay; NHEJ reporter assay Oncogene Medium 27721405
2017 XRCC5 (Ku80) binds to the COX-2 gene promoter in colon cancer cells and cooperates with p300. p300 acetylates XRCC5 (requires HAT domain) and co-localizes with XRCC5 in the nucleus. Knockdown of XRCC5 suppresses COX-2 promoter activity and reduces colon cancer tumor growth in xenografts. Streptavidin-agarose pulldown; mass spectrometry; co-immunoprecipitation; immunofluorescence; siRNA knockdown; reporter assay; xenograft mouse model PloS one Medium 29049411
2018 Crystal structures of Ku-binding motifs (KBM) of APLF (A-KBM) and XLF (X-KBM) bound to a Ku-DNA complex reveal that both KBMs bind remote sites on the Ku80 alpha/beta domain. The X-KBM occupies an internal pocket formed by a large outward rotation of the Ku80 alpha/beta domain. Mutation of the X-KBM and A-KBM binding sites in Ku80 compromises NHEJ efficiency, accuracy, and increases radiosensitivity. X-ray crystallography of Ku-DNA-KBM complexes; APLF/XLF laser-irradiation foci assay; NHEJ functional assay; radiation sensitivity assay Nature structural & molecular biology High 30291363
2018 UCHL3 deubiquitylates Ku80 directly and interacts with Ku80. Depletion of UCHL3 reduces Ku80 foci formation and chromatin binding after DSB induction, impairs NHEJ, and increases HR. DNA damage induces ATM-dependent phosphorylation of UCHL3, which destabilizes UCHL3 without affecting its catalytic activity. Co-immunoprecipitation; deubiquitylase activity assay; Ku80 foci analysis; NHEJ and HR reporter assays; ionizing radiation sensitivity assay Scientific reports Medium 30559450
2019 OTUD5 is a specific deubiquitinase for Ku80 that increases Ku80 stability. OTUD5 depletion impairs NHEJ repair and facilitates HR repair during S/G2 phase by promoting excess end resection, establishing OTUD5 as a positive regulator of NHEJ through Ku80 deubiquitylation. Co-immunoprecipitation; in vitro deubiquitylase activity assay; NHEJ/HR reporter assays; DNA end resection assay Cellular and molecular life sciences Medium 30980112
2019 Ku80 binds to the PDK1 promoter and activates PDK1 transcription in a HIF1-α-dependent manner. Melatonin degrades HIF1-α, reduces Ku80 binding at PDK1 promoter, and inhibits PDK1 expression, suppressing melanoma growth. ChIP; siRNA knockdown and overexpression; promoter reporter assay; xenograft mouse model Redox biology Medium 31023624
2019 The Ku80 von Willebrand antigen domain (vWA) supports a conserved binding site for the KBM motifs of APLF, MRI, and WRN. Structural characterization by NMR/X-ray crystallography defines these interactions. The KBMX (XLF-type) binding site on the vWA domain is occluded and only accessible conditionally. X-ray crystallography of isolated Ku80 vWA domain with KBM peptides; fluorescence polarization; 19F NMR DNA repair High 31733588
2020 The Ku80 C-terminal extension contributes to DNA-PK complex stability but is not absolutely required for its formation. The Ku70 C-terminal SAP domain is required for stable Ku70/Ku80 association with DNA ends, but this requirement is abrogated in the DNA-PK holocomplex. FRET assay (ECFP-Ku70/EYFP-Ku80); surface plasmon resonance; DNA-PK holocomplex reconstitution; C-terminal deletion mutants International journal of molecular sciences Medium 32937838
2022 DCLK1 kinase binds and phosphorylates XRCC5 (Ku80), which in turn transcriptionally activates COX-2 expression and enhances prostaglandin E2 production, generating an inflammatory tumor microenvironment and promoting colorectal cancer aggressiveness. Proteomics identification of DCLK1 binding partners; co-immunoprecipitation; kinase assay; COX-2 reporter; in vivo mouse CRC model Theranostics Medium 35910805
2025 Ku80 K568 is crotonylated by PCAF. Upon DNA damage, HDAC8 decrotonylates K568, freeing the site for SUMOylation by CBX4. This conversion from crotonylation to SUMOylation facilitates DNA-PK complex assembly and DNA-PKcs S2056 autophosphorylation, activating DSB repair. Disruption of K568 PTM sensitizes tumors to radiotherapy in vivo. Quantitative lysine crotonylome mass spectrometry; site-directed mutagenesis; co-immunoprecipitation; DNA-PKcs autophosphorylation assay; xenograft tumor radiotherapy model Signal transduction and targeted therapy High 40254688
1992 Ku80 migrates from the nucleoplasm into nucleoli in a cell cycle-dependent manner, reaching maximum nucleolar accumulation at late S or G2 phase, with minimal nucleolar Ku80 at the G1/S boundary. Immunofluorescence of synchronized HeLa cells; Western blot Experimental cell research Low 1544368

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1994 Ku80: product of the XRCC5 gene and its role in DNA repair and V(D)J recombination. Science (New York, N.Y.) 605 8073286
1996 Requirement for Ku80 in growth and immunoglobulin V(D)J recombination. Nature 556 8700231
2000 DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation. Nature 451 10761921
1996 Ku86-deficient mice exhibit severe combined immunodeficiency and defective processing of V(D)J recombination intermediates. Cell 370 8756720
1999 Deletion of Ku86 causes early onset of senescence in mice. Proceedings of the National Academy of Sciences of the United States of America 301 10485901
2000 Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO reports 269 11256607
1998 Ku80 is required for immunoglobulin isotype switching. The EMBO journal 263 9545251
1998 Double-strand break repair in Ku86- and XRCC4-deficient cells. Nucleic acids research 194 9826756
2002 Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. The EMBO journal 175 11980718
2002 Ku86 is essential in human somatic cells. Proceedings of the National Academy of Sciences of the United States of America 161 11792868
1997 Molecular and biochemical characterization of xrs mutants defective in Ku80. Molecular and cellular biology 158 9032253
1999 The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit. Molecular and cellular biology 152 10207052
2009 Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86. British journal of cancer 140 19672258
1997 Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions. The EMBO journal 139 9362500
2009 Ku86 represses lethal telomere deletion events in human somatic cells. Proceedings of the National Academy of Sciences of the United States of America 137 19581589
2008 Ku80 removal from DNA through double strand break-induced ubiquitylation. The Journal of cell biology 123 18678709
2006 Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO reports 105 17159921
1996 Protein-protein and protein-DNA interaction regions within the DNA end-binding protein Ku70-Ku86. Molecular and cellular biology 104 8756676
2002 Synergistic role of Ku80 and poly(ADP-ribose) polymerase in suppressing chromosomal aberrations and liver cancer formation. Cancer research 100 12460917
2002 Dimerization, translocation and localization of Ku70 and Ku80 proteins. Journal of radiation research 98 12518983
2018 XLF and APLF bind Ku80 at two remote sites to ensure DNA repair by non-homologous end joining. Nature structural & molecular biology 92 30291363
2007 Epigenetic inactivation of the chromosomal stability control genes BRCA1, BRCA2, and XRCC5 in non-small cell lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 91 17289874
2006 Ionizing radiation activates IGF-1R triggering a cytoprotective signaling by interfering with Ku-DNA binding and by modulating Ku86 expression via a p38 kinase-dependent mechanism. Oncogene 86 17043647
2002 Expression of Ku70 and Ku80 mediated by NF-kappa B and cyclooxygenase-2 is related to proliferation of human gastric cancer cells. The Journal of biological chemistry 85 12324457
2019 Partial inhibition of the overactivated Ku80-dependent DNA repair pathway rescues neurodegeneration in C9ORF72-ALS/FTD. Proceedings of the National Academy of Sciences of the United States of America 75 31019093
2005 DNA damage response and Ku80 function in the vertebrate embryo. Nucleic acids research 69 15914672
2004 Impact of telomerase ablation on organismal viability, aging, and tumorigenesis in mice lacking the DNA repair proteins PARP-1, Ku86, or DNA-PKcs. The Journal of cell biology 68 15545322
1992 Localization of a DNA repair gene (XRCC5) involved in double-strand-break rejoining to human chromosome 2. Proceedings of the National Academy of Sciences of the United States of America 66 1631138
2005 Involvement of KU80 in T-DNA integration in plant cells. Proceedings of the National Academy of Sciences of the United States of America 65 16380432
2008 The Ku80 carboxy terminus stimulates joining and artemis-mediated processing of DNA ends. Molecular and cellular biology 56 19103741
1997 Ku86 is not required for protection of signal ends or for formation of nonstandard V(D)J recombination products. Molecular and cellular biology 54 9121473
2002 An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Cancer research 53 12384553
2013 Clinicopathological significance of KU70/KU80, a key DNA damage repair protein in breast cancer. Breast cancer research and treatment 52 23624778
2007 Variation in DNA repair genes XRCC3, XRCC4, XRCC5 and susceptibility to myeloma. Human molecular genetics 52 17901044
2015 Ku80 cooperates with CBP to promote COX-2 expression and tumor growth. Oncotarget 47 25797267
2003 Function of DNA-protein kinase catalytic subunit during the early meiotic prophase without Ku70 and Ku86. Biology of reproduction 47 12604618
1996 Characterization of a Ku86 variant protein that results in altered DNA binding and diminished DNA-dependent protein kinase activity. The Journal of biological chemistry 47 8662896
2018 The deubiquitylating enzyme UCHL3 regulates Ku80 retention at sites of DNA damage. Scientific reports 46 30559450
2013 Genetic polymorphisms in DNA repair genes XRCC4 and XRCC5 and aflatoxin B1-related hepatocellular carcinoma. Epidemiology (Cambridge, Mass.) 45 23788213
2008 Evidence for Ku70/Ku80 association with full-length RAG1. Nucleic acids research 45 18281312
1997 KARP-1: a novel leucine zipper protein expressed from the Ku86 autoantigen locus is implicated in the control of DNA-dependent protein kinase activity. The EMBO journal 44 9214634
2012 Ku80 is highly expressed in lung adenocarcinoma and promotes cisplatin resistance. Journal of experimental & clinical cancer research : CR 42 23181744
2004 Role of human Ku86 in telomere length maintenance and telomere capping. Cancer research 42 15492246
2001 Early decrease in dna repair proteins, Ku70 and Ku86, and subsequent DNA fragmentation after transient focal cerebral ischemia in mice. Stroke 42 11387505
2000 Transfer of Ku86 RNA antisense decreases the radioresistance of human fibroblasts. Cancer gene therapy 42 10770645
2000 Ku86 variant expression and function in multiple myeloma cells is associated with increased sensitivity to DNA damage. Journal of immunology (Baltimore, Md. : 1950) 40 11086072
2018 Suppressing Ku70/Ku80 expression elevates homology-directed repair efficiency in primary fibroblasts. The international journal of biochemistry & cell biology 39 29655920
2013 Ku70 and ku80 null mutants improve the gene targeting frequency in Monascus ruber M7. Applied microbiology and biotechnology 39 23546425
1998 KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion. Proceedings of the National Academy of Sciences of the United States of America 39 9636207
2011 Ku80 gene is related to non-homologous end-joining and genome stability in Aspergillus niger. Current microbiology 36 21225265
2007 Accumulation of Ku80 proteins at DNA double-strand breaks in living cells. Experimental cell research 36 18164703
2006 Ku80 and p53 suppress medulloblastoma that arise independent of Rag-1-induced DSBs. Oncogene 34 16751807
2022 circPRKAA1 activates a Ku80/Ku70/SREBP-1 axis driving de novo fatty acid synthesis in cancer cells. Cell reports 33 36417875
2011 Genetic polymorphisms in DNA double-strand break repair genes XRCC5, XRCC6 and susceptibility to hepatocellular carcinoma. Carcinogenesis 33 21304054
2022 DCLK1 promotes colorectal cancer stemness and aggressiveness via the XRCC5/COX2 axis. Theranostics 32 35910805
2005 Decreased origin usage and initiation of DNA replication in haploinsufficient HCT116 Ku80+/- cells. Journal of cell science 32 16014376
2002 Translocation of Ku86/Ku70 to the multiple myeloma cell membrane: functional implications. Experimental hematology 32 11882358
2001 Hypoxia-activated ligand HAL-1/13 is lupus autoantigen Ku80 and mediates lymphoid cell adhesion in vitro. American journal of physiology. Cell physiology 31 11245607
2019 The deubiquitinase OTUD5 regulates Ku80 stability and non-homologous end joining. Cellular and molecular life sciences : CMLS 29 30980112
2003 Selective inhibition of class switching to IgG and IgE by recruitment of the HoxC4 and Oct-1 homeodomain proteins and Ku70/Ku86 to newly identified ATTT cis-elements. The Journal of biological chemistry 28 12672812
1994 Regional assignment of a human DNA repair gene (XRCC5) to 2q35 by X-ray hybrid mapping. Genomics 28 8088837
2014 Alternative splicing of FBP-interacting repressor coordinates c-Myc, P27Kip1/cyclinE and Ku86/XRCC5 expression as a molecular sensor for bleomycin-induced DNA damage pathway. Oncotarget 27 24811221
2017 XRCC5 cooperates with p300 to promote cyclooxygenase-2 expression and tumor growth in colon cancers. PloS one 26 29049411
2005 Ku86 preserves chromatin integrity in cells adapted to high NaCl. Proceedings of the National Academy of Sciences of the United States of America 26 16027367
2010 Multistudy fine mapping of chromosome 2q identifies XRCC5 as a chronic obstructive pulmonary disease susceptibility gene. American journal of respiratory and critical care medicine 25 20463177
2016 EAF2 regulates DNA repair through Ku70/Ku80 in the prostate. Oncogene 24 27721405
2005 The Ku70-binding site of Ku80 is required for the stabilization of Ku70 in the cytoplasm, for the nuclear translocation of Ku80, and for Ku80-dependent DNA repair. Experimental cell research 24 15817152
2020 Lignocellulose hydrolytic enzymes production by Aspergillus flavus KUB2 using submerged fermentation of sugarcane bagasse waste. Mycology 23 34026303
2011 Role of the XRCC5/XRCC6 dimer in carcinogenesis and pharmacogenomics. Pharmacogenomics 23 21521024
2011 Expression of XRCC5 in peripheral blood lymphocytes is upregulated in subjects from a heavily polluted region in the Czech Republic. Mutation research 23 21684294
2003 Expression of Ku86 confers favorable outcome of tonsillar carcinoma treated with radiotherapy. Head & neck 23 12658736
1992 Cell cycle-dependent migration of the DNA-binding protein Ku80 into nucleoli. Experimental cell research 23 1544368
2015 Analysis of difference of association between polymorphisms in the XRCC5, RPA3 and RTEL1 genes and glioma, astrocytoma and glioblastoma. American journal of cancer research 22 26328260
2008 Ku80 deletion suppresses spontaneous tumors and induces a p53-mediated DNA damage response. Cancer research 22 19010925
2004 Effect of Ku86 and DNA-PKcs deficiency on non-homologous end-joining and homologous recombination using a transient transfection assay. Mutation research 22 15450431
2019 Ku80 promotes melanoma growth and regulates antitumor effect of melatonin by targeting HIF1-α dependent PDK-1 signaling pathway. Redox biology 21 31023624
2012 Serum anti-Ku86 is a potential biomarker for early detection of hepatitis C virus-related hepatocellular carcinoma. Biochemical and biophysical research communications 21 22554520
1992 Assignment of a human DNA double-strand break repair gene (XRCC5) to chromosome 2. Genomics 21 1505945
2013 Drosophila UTX coordinates with p53 to regulate ku80 expression in response to DNA damage. PloS one 20 24265704
2008 Activities of DNA-PK and Ku86, but not Ku70, may predict sensitivity to cisplatin in human gliomas. Journal of neuro-oncology 20 18415044
2005 Heterozygous inactivation of human Ku70/Ku86 heterodimer does not affect cell growth, double-strand break repair, or genome integrity. DNA repair 20 16325483
2004 Characterization of proteins binding to E-box/Ku86 sites and function of Ku86 in transcriptional regulation of the human xanthine oxidoreductase gene. The Journal of biological chemistry 20 14761964
2004 Polyethyleneimine grafted with pluronic P85 enhances Ku86 antisense delivery and the ionizing radiation treatment efficacy in vivo. Gene therapy 20 15470482
2015 Ku80 Counters Oxidative Stress-Induced DNA Damage and Cataract Formation in the Human Lens. Investigative ophthalmology & visual science 19 26658510
2004 Expression of DNA-PKcs and Ku86, but not Ku70, differs between lymphoid malignancies. Experimental and molecular pathology 19 15215044
2002 Differential expression of DNA nonhomologous end-joining proteins Ku70 and Ku80 in melanoma progression. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 11950917
2014 Association between polymorphisms at promoters of XRCC5 and XRCC6 genes and risk of breast cancer. Medical oncology (Northwood, London, England) 18 24615008
2007 Silencing Ku80 using small interfering RNA enhanced radiation sensitivity in vitro and in vivo. International journal of oncology 18 17487369
2022 Integrated analysis reveals FOXA1 and Ku70/Ku80 as targets of ivermectin in prostate cancer. Cell death & disease 17 36050295
2020 miR-623 suppresses cell proliferation, migration and invasion through direct inhibition of XRCC5 in breast cancer. Aging 17 32501811
2020 C-Terminal Extensions of Ku70 and Ku80 Differentially Influence DNA End Binding Properties. International journal of molecular sciences 17 32937838
2015 Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 17 25937401
2012 PMA-induced dissociation of Ku86 from the promoter causes transcriptional up-regulation of histamine H(1) receptor. Scientific reports 17 23209876
2001 Heat-induced aggregation of XRCC5 (Ku80) in nontolerant and thermotolerant cells. Radiation research 17 11741501
2022 Targeting the radiation-induced ARv7-mediated circNHS/miR-512-5p/XRCC5 signaling with Quercetin increases prostate cancer radiosensitivity. Journal of experimental & clinical cancer research : CR 16 35918767
2019 Ligand binding characteristics of the Ku80 von Willebrand domain. DNA repair 16 31733588
2004 Ku70/Ku80 and DNA-dependent protein kinase catalytic subunit modulate RAG-mediated cleavage: implications for the enforcement of the 12/23 rule. The Journal of biological chemistry 16 15123719
2000 Human colon carcinoma cell-line HCT116 transfected by antisense cDNA as a tool to study the Ku86 involvement in cell proliferation. Cellular signalling 16 11152960
2025 Conversion of Ku80 K568 crotonylation to SUMOylation facilitates DNA non-homologous end joining and cancer radioresistance. Signal transduction and targeted therapy 15 40254688
2019 JmjC domain-containing protein 8 (JMJD8) represses Ku70/Ku80 expression via attenuating AKT/NF-κB/COX-2 signaling. Biochimica et biophysica acta. Molecular cell research 15 31473257

Missed literature

Know a paper Affinage missed for XRCC5? Flag it for the maintainers and the community.

No submissions yet.