{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Nie Chen"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-15822"],"description":["Genomic integrity within transcriptionally active regions is crucial for averting oncogenic mutations, yet the precise mechanisms governing DNA double-strand break (DSB) repair in these areas remain elusive. This study reveals that the IRAK1-spliceosome axis orchestrates small nuclear RNA (snRNA) as a central molecular hub, potently activating the ATM at DSB sites within active chromatin to enable precise repair. Mechanistically, IRAK1 phosphorylates spliceosomal SR proteins to recruit snRNA to DSBs, inducing condensation of the MRN complex near transcriptionally active regions to create an ATM activation platform. Inhibition of the IRAK1-spliceosome-snRNA axis compromises ATM activation at damaged sites in active regions, leading to increased mutations exclusively within these regions and"],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sample Collection - Each group was prepared with 2x107 cells. As for DIvA U2OS stable cells, cells were treated with IRAK1 inhibitor for 13 hours, followed by the addition of 300 nM 4-hydroxytamoxifen (4OHT) and treated for 1 hour to induce DSBs. As for iCUT HeLa stable cells, cells were treated with IRAK1 inhibitor for 17.5 hours, followed by the addition of 1 μM 4OHT and treated for 5 hours to induce DSBs.","Nucleic Acid Extraction - Cells were gently scraped from the culture dishes using a cell scraper, washed twice with PBS, and fixed with 1% formaldehyde in PBS at room temperature for 10 minutes, then quenched by incubation with 0.125 M glycine for 5 minutes. Cells were washed once with PBS and lysed sequentially using Buffer 1 (50 mM HEPES, pH 7.5; 140 mM NaCl; 1 mM EDTA, pH 8.0; 10% glycerol; 0.5% NP-40; 0.25% Triton X-100) and Buffer 2 (200 mM NaCl; 1 mM EDTA; 0.5 mM ethylene glycol-bis(b-aminoethyl ether)-N,N,N’,N’-tetraacetic acid (EGTA); 10 mM Tris-HCl, pH 8.0) at 4 °C with rotation for 10 minutes each. After centrifugation, pellets were treated with lysis buffer (1% SDS, 10 mM EDTA, 50 mM Tris-HCl, pH 8.0). All buffers used contained 1 mM PMSF, 0.6-2 mg/mL aprotinin, and 1x protein p","Sequencing - Libraries were pooled and sequenced on Illumina platforms with PE150 by Novogene.","Library Construction - ChIP-seq library preparation was proceeded as follows: the DNA fragments were end-repaired and A-tailed, then ligated with sequencing adaptors; the final DNA library was obtained after size selection and PCR amplification."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Data Transformation - The BAM files were converted to bigwig files using deepTools.","Sequence Alignment - Raw data was processed using Trim-Galore for quality control and adapter trimming. Subsequently, reads were aligned to the hg38 genome using HISAT2. Duplicate reads were removed using Sambamba, and the resulting alignments were sorted into a BAM format with SAMtools. For samples from replicate groups, duplicate reads were merged before further analysis."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq 6000"],"study_type":["ChIP-seq"],"species":["Homo sapiens"],"pubmed_authors":["Nie Chen","Wang Jiadong"],"additional_accession":[]},"is_claimable":false,"name":"snRNA Orchestrates ATM Activation to Promote Accurate Repair within Transcriptionally Active Chromatin (ChIP-seq)","description":"Genomic integrity within transcriptionally active regions is crucial for averting oncogenic mutations, yet the precise mechanisms governing DNA double-strand break (DSB) repair in these areas remain elusive. This study reveals that the IRAK1-spliceosome axis orchestrates small nuclear RNA (snRNA) as a central molecular hub, potently activating the ATM at DSB sites within active chromatin to enable precise repair. Mechanistically, IRAK1 phosphorylates spliceosomal SR proteins to recruit snRNA to DSBs, inducing condensation of the MRN complex near transcriptionally active regions to create an ATM activation platform. Inhibition of the IRAK1-spliceosome-snRNA axis compromises ATM activation at damaged sites in active regions, leading to increased mutations exclusively within these regions and","dates":{"release":"2026-08-31T00:00:00Z","modification":"2026-08-31T01:00:55.043Z","creation":"2025-10-22T15:30:54.578Z"},"accession":"E-MTAB-15822","cross_references":{"ENA":["ERP182722"],"EFO":["EFO_0002944","EFO_0004170","EFO_0002692","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184"]}}