MRE11A Antibody
- Known as:
- MRE11A Antibody
- Catalog number:
- csb-pa014786esr1hu
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- CusAb
- Gene target:
- MRE11A Antibody
Related genes to: MRE11A Antibody
- Gene:
- MRE11 NIH gene
- Name:
- MRE11 homolog, double strand break repair nuclease
- Previous symbol:
- MRE11A
- Synonyms:
- ATLD
- Chromosome:
- 11q21
- Locus Type:
- gene with protein product
- Date approved:
- 1995-05-05
- Date modifiied:
- 2019-04-23
Related products to: MRE11A Antibody
Related articles to: MRE11A Antibody
- Aging, or organismal senescence, is a gradual decline that begins in adulthood, leading to functional loss and an increased risk of disease. Genomic instability and telomere shortening are primary hallmarks associated with aging. Mre11, crucial for DNA damage repair and telomere maintenance, is a potential biomarker of aging. The silkworm, Bombyx mori, is an ideal model for life science research due to its similarities to humans and experimental advantages (well-annotated genome, short life cycle, and appropriate body size). Mre11 is highly conserved across species. In this study, we embarked on establishing the aging silkworm model and evaluated the etiology. Firstly, we constructed Mre11 homozygous mutants by the CRISPR/Cas9 system. Further examination showed that BmMre11 deficiency successfully induced senescence in the fat body. Furthermore, transcriptome and lipidomics analyses indicated that dysregulation of mitochondrial and lipid metabolism is associated with fat body senescence. This work expands our understanding of Mre11's functions in insect metabolism and aging, offering a promising model for fat body aging research. - Source: PubMed
Publication date: 2026/06/22
Yang DehongZhang LiyingChen DongbinGu YaozhiWei XiangyiPi HuihuiSun JunlongHuang YongpingLi Kai - STING is an innate immune adaptor, classically activated by cytosolic DNA via cGAS-cGAMP to induce interferon signaling. Recent studies reveal that STING participates in non-canonical signaling pathways and localizes to the nucleus, where its functions remain poorly understood. In Hutchinson-Gilford Progeria Syndrome (HGPS), a premature aging disease caused by expression of the lamin-A mutant protein 'progerin', STING accumulates in the nucleus and drives chronic inflammation. Here, we show that replication stress is a trigger of STING nuclear accumulation and chromatin binding. In addition, we uncover that STING binds to nascent DNA and promotes replication stress in progeria and tumor cells. Mechanistically, STING causes replication fork slowing and stalling by limiting dNTPs availability. Upon fork stalling, STING hinders replication fork protection/stability by facilitating MRE11-mediated nascent DNA degradation (NDD). Importantly, STING's contribution to dNTP depletion and NDD is mediated by SAMHD1. Depletion of SAMHD1 phenocopies STING abrogation in reducing replication stress in progeria cells, and rescues replication fork speed and stability in STING-expressing tumor cells. These findings define a pathological STING-SAMHD1 axis that drives replication stress and genome instability in both progeria cells and tumor cells with elevated STING activity, uncovering a feedforward loop between innate immune signaling and impaired DNA replication. - Source: PubMed
Teodoro-Castro Barbarade Faria Rafael CancadoShashkova Elena VMalique AtikaAdolph Madison BSilva Lilian N DGonzalo Susana - Inhibition of DNA polymerase theta (Polθ), an essential enzyme for repairing DNA double-strand breaks (DSBs) via microhomology-mediated end joining (MMEJ), has proven to be an exquisitely effective monotherapy in HR-deficient tumor models. In addition, Polθ inhibition (Polθi) can induce tumor-selective radiosensitization, but unlike its monotherapy use, no clinically actionable biomarkers have yet been identified to predict this effect. Here, we profiled 54 cancer cell lines and found that Polθi induces substantial radiosensitization in most models, although with marked variability not explained by indicators of Polθ activity. To pinpoint molecular determinants of radiosensitization by Polθi, we performed a CRISPR knockout screen which revealed loss of the TP53BP1/Shieldin pathway component () as a vulnerability to Polθi combined with RT. We found that is deleted in a subset of human prostate cancers, frequently alongside loss, an adverse prognostic factor. We demonstrated that loss not only increases sensitivity to RT alone, as reported previously, but also enhances the radiosensitizing effect of Polθi, independently of status and without requiring HR deficiency. Moreover, our findings support a model in which deficiency increases Polθ dependence following RT, with Polθ activity limiting DSB accumulation and chromosomal instability, via a compensatory mechanism independent of canonical MRE11/CtIP-mediated DNA end resection. In summary, we found that loss is a collateral vulnerability that can be exploited through combined treatment with Polθi and RT. - Source: PubMed
Publication date: 2026/06/12
Rodriguez-Berriguete GonzaloThambiayah PurusothaCicconi AlessandroMachado NicoleGotorbe CeliaNderitu DavidCheng Wei-ChenFowler GerissaBoursier Marie LaureCerutti AuroraGrinkevich VeraHill Bethany RebekahKoler KatjušaLangdon Sophie AliceMajithiya Jayesh BMenon SurajMoore ShaunNeves JoanaPalmer-Deverill Natalie MRajendra EesonRoy-Luzarraga MarinaThapa AsmitaHeald Robert ASmith Graeme C MRobinson Helen M RRanzani MarcoHiggins Geoff S - The R2TP chaperone complex comprises two AAA+ proteins, RUVBL1 and RUVBL2, along with RPAP3 and PIH1D1. R2TP functions in concert with other chaperones, such as HSP90 and HSP70, to facilitate the assembly of macromolecular complexes integral to the regulation of cell growth and proliferation. Moreover, several adaptors interact with R2TP to impart substrate specificity. Nevertheless, the precise mechanism underlying R2TP-mediated complex assembly remains unknown. This review summarizes the current knowledge regarding R2TP's involvement in the assembly, stabilization, and activity of multiple protein complexes, including box C/D and H/ACA small nucleolar ribonucleoproteins (snoRNPs), spliceosome small nuclear ribonucleoproteins (snRNPs), the tuberous sclerosis complex (TSC) , axonemal dynein arms, RNA polymerases, phosphatidylinositol 3-kinase-related kinases (PIKK), and the MRE11-RAD50-NBS1 (MRN) complex. Additionally, the role of R2TP in ciliogenesis, circadian rhythm regulation, and transcriptional condensate formation is discussed. Finally, the latest structural studies pertaining to R2TP and its related complexes are examined. - Source: PubMed
Publication date: 2026/06/04
Mohamed MaryamaWu RuikaiHoury Walid A - PARPi are effective therapy for BRCA1/2 mutant cancers, yet recurrent PARPi resistance frequently develops. The underlying mechanism of PARPi resistance remains largely unresolved. Here, we identify STN1, a component of the CTC1/STN1/TEN1 (CST) complex, as a modulator of PARPi resistance in BRCA2-deficient cells. RNA-seq analysis of PARPi-resistant cancer cells from BRCA2-mutated backgrounds shows largely distinct transcriptomic profiles with limited overlap, suggesting multiple routes to resistance. Notably, STN1 is consistently upregulated in resistant cells. We observe that overexpression of STN1 enhances Olaparib resistance in multiple BRCA2-deficient cell lines and alleviates DNA damage under replication stress. Mechanistically, we find that STN1 overexpression increases RAD51 loading to stalled replication forks while restricting MRE11 recruitment in BRCA2-deficient cells, thereby protecting stalled forks from nascent-strand degradation. Furthermore, STN1 overexpression rescues the accumulation of ssDNA gaps, a major determinant of PARPi sensitivity in BRCA2-deficient cells. Taken together, these findings suggest that elevated STN1 levels can partially compensate for BRCA2 loss by stabilizing stalled replication forks and limiting ssDNA gap accumulation. Our study uncovers a STN1-dependent pathway of replication stress tolerance that promotes PARPi resistance independently of homologous recombination restoration, highlighting STN1 as a potential biomarker and mechanistic contributor to therapeutic resistance in BRCA2-mutated cancers. - Source: PubMed
Publication date: 2026/05/19
Laghari Zubair AhmedLi NaWang Qi-EnChai Weihang