Ask about this productRelated genes to: XRCC5 antibody
- Gene:
- XRCC5 NIH gene
- Name:
- X-ray repair cross complementing 5
- Previous symbol:
- -
- Synonyms:
- KU80, KARP-1, Ku86, KUB2
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 1992-01-22
- Date modifiied:
- 2016-06-02
Related products to: XRCC5 antibody
Related articles to: XRCC5 antibody
- In mammalian cells, DNA double-strand breaks (DSBs) are repaired by two competing pathways-homologous recombination (HR) and non-homologous end-joining (NHEJ)-that act on the same DNA ends. Downregulation of NHEJ has been shown to enhance HR-mediated repair. Macular corneal dystrophy (MCD) is an autosomal recessive disorder characterized by progressive corneal opacity and vision loss in humans. More than 180 mutations in the CHST6 gene are linked to MCD, with over 70% occurring in exon 3, making it a promising target for genome editing. In this study, we performed in vitro editing of exon 3 of CHST6 using CRISPR/Cas9 in Human Embryonic Kidney (HEK293) cells. To promote HR, the NHEJ genes XRCC6 and XRCC5, encoding KU70 and KU80, were knocked down individually or in combination. A homologous donor template was also introduced, and HR efficiency was assessed by Western blot analysis. Results demonstrated a significant increase in HR activity following downregulation of these NHEJ components, as indicated by elevated RAD51 expression. As proof of concept, partial restoration of CHST6 protein expression was observed in edited cells compared with CHST6 knockdown controls after suppression of XRCC6 and XRCC5 along with donor template delivery. These findings suggest that targeting NHEJ to enhance HR may represent a promising therapeutic strategy for MCD. - Source: PubMed
Publication date: 2026/07/13
Baruah AparajitaWimmer TobiasStieger KnutPonnam Surya Prakash Goud - Anaplastic thyroid carcinoma (ATC) is an exceptionally aggressive malignancy with dismal survival, largely due to intrinsic cisplatin resistance. This study identifies a novel mechanism by which small extracellular vesicles (sEVs) promote chemoresistance by enhancing DNA repair via protein lactylation. ATC cells secrete sEVs enriched with Annexin A2 (ANXA2). Upon delivery to recipient ATC cells, ANXA2 stabilizes the interaction between SRC kinase and lactate dehydrogenase A (LDHA), leading to increased LDHA phosphorylation (Y10), enzyme activity, and lactate production. The resulting lactate surge serves as a substrate for lysine lactylation. Ku80 (XRCC5) is identified as a key lactylation target at K265, catalyzed by the acyltransferase KAT5. This lactylation modification strengthens the interaction between Ku80 and its partner Ku70 (XRCC6), stabilizing the initial DNA-end binding complex in the non-homologous end-joining (NHEJ) repair pathway. Consequently, NHEJ efficiency is significantly enhanced, enabling ATC cells to rapidly repair cisplatin-induced DNA double-strand breaks and survive treatment. Genetic disruption of the XRCC5-K265 lactylation site or pharmacological inhibition of LDHA sensitizes ATC xenograft tumors to cisplatin, while in vitro, inhibition of the SRC/LDHA axis produces a similar chemosensitizing effect. This work unveils the ANXA2 sEV/SRC/LDHA/lactate/XRCC5-lactylation axis as a critical driver of NHEJ-mediated chemoresistance in ATC, offering new potential therapeutic targets. - Source: PubMed
Publication date: 2026/07/03
Su ShanshanXiong YiShanLiang YuxuanMin XiangDai Daofeng - DNA double-strand breaks (DSBs) represent a major threat to genomic integrity. DSBs are primarily repaired through homologous recombination (HR) and non-homologous end-joining (NHEJ). The Ku complex, composed of XRCC5 and XRCC6, initiates NHEJ by binding to the DNA ends in DSBs. Our previous study demonstrated that FOXL2 regulates Ku availability through acetylation-dependent interaction; however, whether related mechanisms operate across other FOX family proteins and how these can be regulated in response to genotoxic stress remain unclear.In this study, we demonstrated that multiple FOX family members interact with XRCC5/6 and acetylation-dependently suppress NHEJ. GCN5 (KAT2A) promoted the acetylation of a conserved lysine residue within the forkhead domain, thereby enhancing FOX-Ku association and limiting Ku availability. In response to DNA damage, SIRT1 underwent SUMOylation at lysine 734, thereby promoting its nuclear accumulation through KPNA2/KPNA3-dependent import. Nuclear SIRT1 acted as a deacetylase and reversed FOX acetylation, thereby reducing FOX-Ku interaction and permitting NHEJ activation.The results of this study define a DNA damage-responsive GCN5-SIRT1 regulatory axis that modulates FOX acetylation, FOX-Ku interaction, and NHEJ activity. Our study extends FOXL2-centered findings and supports a shared, but context-dependent, DNA repair regulation-supporting mechanism involving multiple FOX proteins. - Source: PubMed
Publication date: 2026/06/20
Luo YongyangLee KangseokBae Jeehyeon - Temozolomide (TMZ) resistance is a major challenge in glioblastoma (GBM). The role of BRCA1-associated RING domain protein 1 (BARD1), a DNA damage response protein, in GBM and its potential link to liquid-liquid phase separation (LLPS) remain unclear. Bioinformatics analysis of TCGA, CGGA, and GEO datasets revealed that high BARD1 expression correlates with poor prognosis in GBM. Functional studies demonstrated that BARD1 knockdown inhibited glioma cell proliferation, migration, and invasion. We discovered that BARD1 undergoes LLPS via its intrinsically disordered region (IDR, aa 113-425). Upon TMZ-induced DNA damage, BARD1 forms nuclear condensates that recruit X-ray repair cross-complementing protein 5 (XRCC5) to damage sites, promoting repair and driving TMZ resistance. Disrupting this phase separation capability impaired DNA repair. Through structure-based virtual screening, our results suggest that Ziprasidone and Apomorphine may disrupt the BARD1-XRCC5 interaction. Combining either compound with TMZ enhanced cytotoxicity in vitro and suppressed tumor growth in vivo. Our findings unveil a novel LLPS-mediated mechanism by which BARD1 confers TMZ resistance in GBM, positioning it as a prognostic marker and a therapeutic target. Targeting the BARD1-XRCC5 axis presents a promising strategy to overcome chemoresistance. - Source: PubMed
Publication date: 2026/06/17
Wang ChaoCheng XingboLiu ZhendongWang YanpingGao YanzhengLiu Yumei - Ribosome biogenesis (RiboSis) serves as an important foundation for the malignant progression of tumors. In this study, bioinformatics was employed to evaluate the association between RiboSis and lung adenocarcinoma (LUAD) and to preliminarily uncover potential therapeutic targets. Analysis of DepMap CRISPR/RNAi data revealed that 73% of RiboSis genes are essential for cancer cell survival. RNA-seq analysis demonstrated that RiboSis remains continuously active in multiple types of tumors and is closely related to unfavorable clinical outcomes. Through Cox and LASSO-Cox regression analyses, DDX56, XRCC5, and FAM207A were identified as risk genes associated with LUAD. We further examined their co-mutation patterns with the top 10 most frequently mutated genes in LUAD. The results revealed a significant co-occurrence phenomenon among these three genes. Enrichment analysis linked these genes to the p53 pathway, cell cycle regulation, and immune cell infiltration. The CellMiner database revealed that these three genes are associated with resistance to multiple anticancer drugs. Subsequently, LUAD cell lines with knockdown of DDX56, XRCC5, and FAM207A, respectively, were constructed. The impacts of these three risk genes on the migration and invasion abilities of tumor cells were evaluated using CCK-8, Transwell, and cell scratch assays. The results showed that the knockdown of these genes could significantly inhibit tumor migration and invasion. In summary, this study preliminarily indicates that DDX56, XRCC5, and FAM207A may be potential therapeutic targets for LUAD, providing new strategies for the clinical treatment of LUAD. - Source: PubMed
Publication date: 2026/06/09
Yin NanchangRen Hong