| Tbio | X-ray repair cross-complementing protein 5 |
Single-stranded DNA-dependent ATP-dependent helicase. 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. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 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 XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:20383123). The XRCC5/6 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 XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488).
The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]
The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]
Comments
Property Summary
| NCBI Gene PubMed Count | 249 |
| Grant Count | 180 |
| R01 Count | 137 |
| Funding | $15,975,988.23 |
| PubMed Score | 456.71 |
| PubTator Score | 369.40 |
| Disease | log2 FC | p |
|---|---|---|
| Waldenstrons macroglobulinemia | 1.568 | 0.002 |
| Multiple myeloma | 1.357 | 0.002 |
| osteosarcoma | -1.130 | 0.007 |
| glioblastoma | 1.600 | 0.011 |
| sonic hedgehog group medulloblastoma | 1.600 | 0.000 |
| atypical teratoid/rhabdoid tumor | 1.400 | 0.000 |
| medulloblastoma, large-cell | 1.500 | 0.000 |
| primitive neuroectodermal tumor | 1.100 | 0.000 |
| acute quadriplegic myopathy | 1.262 | 0.000 |
| lung cancer | 1.500 | 0.000 |
| breast carcinoma | 1.500 | 0.004 |
| Breast cancer | 2.700 | 0.036 |
| pediatric high grade glioma | 1.300 | 0.000 |
| ovarian cancer | 2.400 | 0.000 |
| PMID | Text |
|---|---|
| 26658510 | 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 |
| 26502055 | Data show that ubiquitin E3 ligase RNF138 regulates Ku80 antigen ubiquitylation in response to DNA damage. |
| 26464705 | 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 |
| 26360636 | HIV-1 MA interacts with XRCC5 (Ku80) |
| 26359349 | 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. |
| 25818292 | 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 |
| 25758053 | 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. |
| 25756210 | Polymorphism in XRCC5 gene is associated with Systemic Lupus Erythematosus. |
| 25702660 | 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. |
| 25527410 | Polymorphisms in the Variable Number of Tandem Repeats at the promoter region of the XRCC5 is associated with gastric cancer. |
| More... |
MVRSGNKAAVVLCMDVGFTMSNSIPGIESPFEQAKKVITMFVQRQVFAENKDEIALVLFGTDGTDNPLSG 1 - 70 GDQYQNITVHRHLMLPDFDLLEDIESKIQPGSQQADFLDALIVSMDVIQHETIGKKFEKRHIEIFTDLSS 71 - 140 RFSKSQLDIIIHSLKKCDISLQFFLPFSLGKEDGSGDRGDGPFRLGGHGPSFPLKGITEQQKEGLEIVKM 141 - 210 VMISLEGEDGLDEIYSFSESLRKLCVFKKIERHSIHWPCRLTIGSNLSIRIAAYKSILQERVKKTWTVVD 211 - 280 AKTLKKEDIQKETVYCLNDDDETEVLKEDIIQGFRYGSDIVPFSKVDEEQMKYKSEGKCFSVLGFCKSSQ 281 - 350 VQRRFFMGNQVLKVFAARDDEAAAVALSSLIHALDDLDMVAIVRYAYDKRANPQVGVAFPHIKHNYECLV 351 - 420 YVQLPFMEDLRQYMFSSLKNSKKYAPTEAQLNAVDALIDSMSLAKKDEKTDTLEDLFPTTKIPNPRFQRL 421 - 490 FQCLLHRALHPREPLPPIQQHIWNMLNPPAEVTTKSQIPLSKIKTLFPLIEAKKKDQVTAQEIFQDNHED 491 - 560 GPTAKKLKTEQGGAHFSVSSLAEGSVTSVGSVNPAENFRVLVKQKKASFEEASNQLINHIEQFLDTNETP 561 - 630 YFMKSIDCIRAFREEAIKFSEEQRFNNFLKALQEKVEIKQLNHFWEIVVQDGITLITKEEASGSSVTAEE 631 - 700 AKKFLAPKDKPSGDTAAVFEEGGDVDDLLDMI 701 - 732 //
| PMID | Year | Title |
|---|---|---|
| 26658510 | 2015 | Ku80 Counters Oxidative Stress-Induced DNA Damage and Cataract Formation in the Human Lens. |
| 26502055 | 2015 | The RNF138 E3 ligase displaces Ku to promote DNA end resection and regulate DNA repair pathway choice. |
| 26496610 | 2015 | A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| 26464705 | 2015 | Blood-based DNA methylation of DNA repair genes in the non-homologous end-joining (NEHJ) pathway in patient with glioma. |
| 26359349 | 2015 | Heat shock factor 1, an inhibitor of non-homologous end joining repair. |
| 25944712 | 2015 | N-terminome analysis of the human mitochondrial proteome. |
| 25941166 | 2015 | XLS (c9orf142) is a new component of mammalian DNA double-stranded break repair. |
| 25852083 | 2015 | DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle cell proliferation through phosphorylation of the orphan nuclear receptor NOR1. |
| 25818292 | 2015 | Direct involvement of retinoblastoma family proteins in DNA repair by non-homologous end-joining. |
| 25758053 | 2015 | Prognostic significance of Ku80 in pT2N0M0 esophageal squamous cell carcinoma after Ivor-Lewis esophagectomy. |
| More... |
