{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/075/SRR12094675/SRR12094675.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR109/039/SRR10969739/SRR10969739.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/044/SRR13258644/SRR13258644.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/078/SRR12094678/SRR12094678.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/072/SRR12094672/SRR12094672.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/049/SRR13258649/SRR13258649.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/041/SRR13258641/SRR13258641.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/013/SRR13082213/SRR13082213.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR109/036/SRR10969736/SRR10969736.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/077/SRR12094677/SRR12094677.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/073/SRR12094673/SRR12094673.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR109/037/SRR10969737/SRR10969737.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/047/SRR13258647/SRR13258647.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/043/SRR13258643/SRR13258643.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/045/SRR13258645/SRR13258645.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR109/035/SRR10969735/SRR10969735.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/048/SRR13258648/SRR13258648.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/040/SRR13258640/SRR13258640.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR109/038/SRR10969738/SRR10969738.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR130/012/SRR13082212/SRR13082212.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/042/SRR13258642/SRR13258642.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/074/SRR12094674/SRR12094674.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR120/076/SRR12094676/SRR12094676.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR132/046/SRR13258646/SRR13258646.fastq.gz"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Martin Eilers, Chair for Biochemistry and Molecular Biology, University of Wuerzburg"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA603314"],"scientific_name":["Homo sapiens"],"long_description":["Targeting the function of MYC proteins for therapy is a major challenge in tumor biology. MYC proteins are transcription factors that can globally release RNA polymerase II (RNAPII) from core promoters. In neuroblastoma, the MYC paralogue, MYCN, and the Aurora-A kinase form a complex during S phase that stabilizes MYCN and enhances Aurora-A kinase activity. Here we show that Aurora-A phosphorylates histone H3 at serine 10 in S phase and suppresses transcription-dependent R-loop formation. Inhibition of Aurora-A causes global stalling of RNAPII at pause sites and exon/intron boundaries and induces transcription/replication conflicts, activating the Ataxia telangiectasia and Rad3 related (ATR) kinase. Activation of ATR is required to prevent the accumulation of double-strand breaks. In genetically-engineered mice with MYCN-driven neuroblastoma, combined inhibition of Aurora-A and ATR induces rampant tumor-specific apoptosis and tumor regression, leading to permanent eradication of tumors in a subset of mice. The therapeutic efficacy is not only due to tumor cell-intrinsic mechanisms, but also engages the host immune system for tumor eradication. Since stabilization of MYCN promotes promoter-proximal transcription termination, we propose that MYCN/Aurora-A complex formation enables tumor cells to prevent transcription-replication conflicts and that targeting this mechanism is an effective therapy for MYCN-driven neuroblastoma. Overall design: S phase synchronized IMR-5 cells treated for 4 h with 1 µM MLN8237 or 1 µM MK5108 or DMSO"],"tag":["xref:PubMed:33768209"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Targeting transcription-replication conflicts is an effective therapeutic principle for MYCN-driven neuroblastoma [ChIP-seq IMR-5]","description":"Targeting transcription-replication conflicts is an effective therapeutic principle for MYCN-driven neuroblastoma [ChIP-seq IMR-5]","dates":{"last_updated":"2025-09-24","first_public":"2020-12-09"},"accession":"PRJNA603314","cross_references":{"GEO":["GSE144284"],"taxon":["9606"],"PubMed":["33768209"]}}