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用途:
For Research Use Only. Not for use in diagnostic or therapeutic procedures.
Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription. In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
基因功能參考文獻(xiàn):
ATM-dependent phosphorylation of CtIP and the epistatic and coordinated actions of MRE11 and CtIP nuclease activities are required to limit the stable loading of Ku on single-ended DNA double-strand breaks. PMID: 27641979
these results suggest that polymorphisms of XRCC5 play an important role in astrocytoma prognosis in the Chinese Han population which could be used in the determination of astrocytoma prognosis in clinical researches PMID: 27852033
SAF-A, in concert with Ku, temporally regulates base damage repair in irradiated cell genome. PMID: 27303920
High XRCC5 expresiion is associated with medullary thyroid carcinoma. PMID: 26870890
Ku80 can be cleaved by caspases-2 at D726 upon a transient etoposide treatment. Caspase-2-mediated Ku80 cleavage promotes Ku80/DNA-PKcs interaction as the D726A mutation diminished Ku80 interaction with DNA-PKcs PMID: 29065392
m-calpain translocated as the result of calcium influx was involved in DNA double-strand breaks repair, especially in the non-homologous end-joining pathway through proteolysis of nuclear Ku80. Cleaved Ku80 was still able to form a heterodimer with Ku70 and enhance DNA repair activity. PMID: 27121057
Ku80 CTR (C-terminal region) is required for interaction with DNA-PKcs on short segments of blunt ended 25bp dsDNA or 25bp dsDNA with a 15-base poly dA ssDNA extension, but this requirement is less stringent on longer dsDNA molecules (35bp blunt ended dsDNA) or 25bp duplex DNA with either a 15-base poly dT or poly dC ssDNA extension. Moreover, DNA-PKcs-Ku complex forms on 25 bp DNA with poly-pyrimidine ssDNA extension. PMID: 28641126
Ku80 could predict the probability of resistance to neoadjuvant chemotherapy in lung adenocarcinoma, and reduced cisplatin and pemetrexed-induced apoptosis in A549 cells PMID: 28399858
results demonstrated that XRCC5 promoted colon cancer growth by cooperating with p300 to regulate COX-2 expression, and suggested that the XRCC5/p300/COX-2 signaling pathway was a potential target in the treatment of colon cancers PMID: 29049411
Ku antigen displays the AP lyase activity on a certain type of double-stranded DNA. PMID: 27129632
Results show that DDB2 is critical for chromatin association of XRCC5/6 in the absence of DNA damage and provide evidence that XRCC5/6 are functional partners of DDB2 in its transcriptional stimulatory activity. PMID: 28035050
RNF126 is a novel regulator of NHEJ that promotes completion of DNA repair by ubiquitylating Ku80 and releasing Ku70/80 from damaged DNA. PMID: 27895153
XRCC5 (rs1051685, rs6941) and AQP2 (10875989, rs3759125) polymorphisms were associated with hematologic toxicity of platinum-based chemotherapy in lung cancer patients PMID: 26358256
Ku80 and PDGFR-alpha might be effective predictive indicators for the prognosis of nasal type NK/T cell lymphoma PMID: 26778387
DNA methylation modification plays an important role to regulate the gene expression of XRCC5 and XRCC7, from the results that the gene methylation level of the glioma group is higher than that of the normal group PMID: 26464705
Data suggest that heat shock factor 1 (HSF1) interacts with both Ku autoantigens Ku70 and Ku86 to induce defective non-homologous end joining (NHEJ) repair activity and genomic instability. PMID: 26359349
The present study showed that the XRCC5 locus might be a contributor to COPD susceptibility in the Chinese Han population. PMID: 24615081
Depletion of Ku80 in the lens through acute change or a consequence of aging is likely to increase levels of DNA strand breaks, which could negatively influence physiological function and promote lens opacity PMID: 26658510
Data show that ubiquitin E3 ligase RNF138 regulates Ku80 antigen ubiquitylation in response to DNA damage. PMID: 26502055
Polymorphisms in the Variable Number of Tandem Repeats at the promoter region of the XRCC5 is associated with gastric cancer. PMID: 25527410
retinoblastoma tumor suppressor protein variants disabled for the interaction with XRCC5 and XRCC6, including a cancer-associated variant, are unable to support canonical non-homologous end-joining despite being able to confer cell-cycle control PMID: 25818292
Genome-wide gene-set-based analysis and follow-up studies in Drosophila and humans generated independent evidence for the involvement of XRCC5 (Ku80) in alcohol dependence PMID: 25035082
Our data indicated that Ku80 expression level associates with key clinicopathological features and is an independent predictor of the OS and the DFS in pT2N0M0 ESCC patients. PMID: 25758053
Polymorphism in XRCC5 gene is associated with Systemic Lupus Erythematosus. PMID: 25756210
both the CG carriers/G allele carriers of rs2267437 (XRCC6) and the haplotype AT/CC established by the SNPs of XRCC5 are associated with ESCC (Esophageal Squamous Cell Carcinoma) susceptibility. PMID: 25702660
the downregulation of Ku80 and an impairment of repair activity in squamous cells, which are mediated by miR-31. PMID: 25082302
RECQL4 stimulates higher order DNA binding of Ku70/Ku80 to a blunt end DNA substrate. Taken together, these results implicate that RECQL4 participates in the NHEJ pathway of DSB repair via a functional interaction with the Ku70/Ku80 complex. PMID: 24942867
High KU86 expression is associated with hepatocellular carcinoma. PMID: 24811221
the VNTR polymorphism at the promoter region of XRCC5, but not XRCC6, may have a role in breast cancer risk or age at diagnosis of breast cancer PMID: 24615008
down-regulation of Ku80 can sensitize ALT cells U2OS to radiation, and this radiosensitization is related to telomere length shortening. PMID: 23621240
the VNTR polymorphism in the promoter region of XRCC5 gene could serve as an important prognostic marker in CML development. PMID: 23982877
Ku86 staining in hepatocellular carcinoma was much stronger than in para-tumor and normal tissues. Expression of Ku86 was related to the tumor size, TNM stage, and tumor differentiation. Long-term survival of patients with low Ku86 expression was longer. PMID: 24271118
Enhanced DNA-PKcs and Ku 70/80 expression may be closely associated with gastric carcinoma. PMID: 24187467
The observations plead in favor of the hypothesis that Ku has an impact on HIV-1 expression and latency at early- and mid-time after integration. PMID: 23922776
For XRCC4P and XRCC5P, only XRCC4P modified liver cancer risk. PMID: 23788213
Processivity factor 8 (PF-8) of Kaposi's sarcoma-associated herpesvirus was identified as interacting with Ku70 and Ku86, and the interaction was dependent on DNA double-strand breaks and DNA. PMID: 23677788
In systemic lupus spectrum diseases, anti-Ku are found associated with other autoantibodies; in systemic sclerosis anti-Ku are frequently associated with myositis and interstitial lung disease. PMID: 23910615
This model highlights the importance of Ku70/80 oxidation which leads to increased Ku70/80 dissociation rates from DNA damage foci and shifts repair in favour of the less efficient Back-up-Non-Homologous End Joining system. PMID: 23457464
The 3R allele of the VNTR polymorphism in the XRCC5 promoter region dramatically decreases the gene expression. PMID: 23220236
Two (XRCC5 and TOP2A) of seven DNA repair and replication proteins studied were prognostic for melanoma. PMID: 23020778
BRCA1-Ku80 protein interaction enhances end-joining fidelity of chromosomal double-strand breaks in the G1 phase of the cell cycle PMID: 23344954
Ku80 expression level could predict the outcome and the sensitivity to cisplatin-based chemotherapy in patients with lung adenocarcinoma PMID: 23181744
Results show the N-terminal region mediates the interaction between DNA-PKcs and the Ku70/Ku80-DNA complex and is required for its DNA double-stranded breaks (DSBs)-induced enzymatic activity. PMID: 23322783
XRCC5 gene polymorphism is associated with breast cancer. PMID: 23098447
It is suggested that the prevalence of the XRCC5 novel allele (3R allele) among European populations may be higher than its prevalence among Iranians. PMID: 23022196
APLF promotes the assembly and activity of multi-protein Ku-DNA complexes containing all of the Non-homologous end joining (NHEJ) factors required for DNA ligation. PMID: 23178593
Data indicate a significant positive association was found between female patients with anti-Ku p70 and joint/bone features, and a significant negative association was found between female patients with anti-Ku p80 only and joint/bone features. PMID: 22226402
Data indicate that dynamic remodeling of the Ku complex coincided with exit of Ku and other DNA repair proteins from the nucleolus. PMID: 22535209
study found Ku80 was downregulated in hepatocellular carcinoma(HCC) and Ku80 downregulation was correlated with elevated HBV-DNA load and liver cirrhosis; suggested an underlying mechanism in which Ku80 functions as a tumor suppressor in HCC by inducing S-phase arrest through a p53-dependent pathway PMID: 22226916
Ku70/80 binds to DNA double strand breaks (DSB) in all cell cycle stages and is likely actively displaced from DSB ends to free the DNA ends for DNA end resection and thus homologous recombination to occur. PMID: 22265216