{"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-15896"],"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 - DIvA cells were treated with IRAK1 inhibitor for 17 hours, following treatment of 300 nM 4OHT for 1 hour. Each sample group was prepared with 1x105 cells and washed once with PBS. For the native group, the subsequent lysis step was performed directly. For the 1,6-Hex+Fix group, the cells were pretreated with 10% 1,6-hexanediol in PBS at room temperature for 30 seconds before fixation. Subsequently, both the 1,6-Hex+Fix and Fix groups were added with 1% formaldehyde in PBS, incubated at room temperature for 10 minutes to fix the cells. The fixation process was quenched by adding glycine to a final concentration of 600 mM, incubated at room temperature for 5 minutes. Finally, the cells were washed once with ice-cold PBS.","Nucleic Acid Extraction - Cells in all groups were treated with 50 µL ATAC-seq RSB (10 mM Tris-HCl pH 7.4, 10 mM NaCl, 3 mM MgCl2) containing 0.1% IGEPAL-630, 0.1% Tween 20, and 0.01% digitonin, on ice for 10 minutes for cell permeabilization. Subsequently, 1 mL RSB containing 0.1% Tween 20 (without IGEPAL-630 or digitonin) was added, and the mixture was gently inverted. The sample was centrifuged at 4 °C for 10 minutes at 500 g, and the pellet was retained. For the native group, the pellet was resuspended with Tn5 transposases (N248, Novoprotein) and tagmentation buffer, followed by incubation at 37 °C for 30 minutes. For the 1,6-Hex+Fix group and Fix group, the pellet was resuspended with Tn5 transposases and tagmentation buffer, followed by incubation at 55 °C for 30 minutes. After tagm","Library Construction - Subsequent library preparation was performed according to the manufacturer’s protocol of High-Sensitivity Open Chromatin Profiling Kit version 2.0 (N248, Novoprotein). The number of PCR cycles was determined by agarose gel electrophoresis. Specifically, 50 µL PCR mixtures were prepared: 1 µL sheared DNA + 1.5 µL N5 primer + 1.5 µL N7 primer + 21 µL ddH2O + 25 µL 1x HiFi AmpliMix, which were gently mixed and separated for three replicate reactions. These reactions were set with different numbers of cycles and underwent PCR amplification, then run on a gel electrophoresis. The number of PCR cycles (n) was set to the value corresponding to the visible band in the gel with the lowest PCR cycle number. For library preparation, the remained 19 µL sheared DNA was used, and ","Sequencing - Libraries were pooled and sequenced on Illumina platforms with PE150 by Novogene."],"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 Fastp for quality control. The cleaned reads were then mapped to the hg38 genome using STAR. Duplicate reads were removed by Sambamba, and the BAM files were sorted. For duplicate samples, reads were merged before subsequent analysis."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq 6000"],"study_type":["ATAC-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 (ACC-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":"2026-08-31T00:59:29.028Z","creation":"2025-10-29T20:49:21.422Z"},"accession":"E-MTAB-15896","cross_references":{"ENA":["ERP183325"],"EFO":["EFO_0002944","EFO_0007045","EFO_0004170","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184"]}}