{"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-15861"],"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":["Library Construction - The genomic DNA was fragmented to approximately 250 bp using the Hieff NGS OnePot Pro DNA Fragmentation Reagent (12619ES, Yeasen). Library preparation was performed with the Hieff NGS DNA Library Prep Kit (13577ES, Yeasen).","Sample Collection - HeLa cells were treated with three regimens: 10 nM CPT; 10 nM CPT + 0.5 µg/mL IRAK1 inhibitor; 10 nM CPT + 1 µM KU-55933 (500 nM Etoposide; 500 nM Etoposide + 0.5 µg/mL IRAK1 inhibitor; 500 nM Etoposide + 1 µM KU-55933). The treatments were administered every other day for two weeks, after which the cells were collected.","Sequencing - Libraries were pooled and sequenced on Illumina platforms with PE150 by Genewiz.","Nucleic Acid Extraction - Genomic DNA was isolated using the MolPure Cell/Tissue DNA Kit (18700ES, Yeasen) according to the manufacturer's protocol."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","Processed Data","MAGE-TAB Files"],"data_protocol":["Sequence Alignment - Raw data underwent quality control and adapter trimming using Trim-Galore, followed by alignment to the hg38 genome using BWA-MEM. The resulting BAM files were sorted for further processing. Subsequently, variant calling was performed using GATK, starting with the removal of duplicate reads by the MarkDuplicates function. Next, BaseRecalibrator function were used to generate a quality score recalibration table, which was then applied using ApplyBQSR function to obtain a corrected BAM file. The Mutect2 function was then used to generate variant call format (VCF) files from the processed data, the parameters were set as follows: disable-read-filter, MateOnSameContigOrNoMappedMateReadFilter; af-of-allelesnot-in-resource, 0.0000025; germline-resource, was af-only-gnomAD VC","Data Transformation - ANNOVAR was employed for functional annotation of the VCF files. The specific mutations in each group were further filtered by comparison to the mutations in the control group. Finally, the mutations in the coding regions are retained for further analysis."],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["Illumina NovaSeq 6000"],"study_type":["DNA-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 (WGRS)","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":"2026-08-31T01:00:12.789Z","creation":"2025-10-24T15:34:07.05Z"},"accession":"E-MTAB-15861","cross_references":{"ENA":["ERP182992"],"EFO":["EFO_0002944","EFO_0004170","EFO_0002693","EFO_0004917","EFO_0005518","EFO_0003816","EFO_0004184"]}}