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Series GSE216874 Query DataSets for GSE216874
Status Public on May 01, 2023
Title Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability [ATAC-Seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Studying the role of circular RNAs in cancer initiation by profiling the interaction of circRNAs with DNA in human cells. The first step of oncogenesis is the acquisition of a repertoire of genetic mutations to initiate and sustain the malignancy. An important example of this initiation phase in leukaemia is the formation of a potent oncogene by chromosomal translocations between the histone methyltransferase Mixed Lineage Leukaemia (MLL) gene and one of over 100 translocation partner genes. Here we show that circular RNAs (circRNAs) - which are a family of covalently-closed, alternatively-spliced RNA molecules - bind DNA, forming circRNA:DNA hybrids (circR-loops) at their cognate loci, and promote transcriptional pausing and DNA breaks. The MLL recombinome concentrates these circR-loops and by overexpressing circRNAs from MLL in human cells we could generate de novo chromosomal translocations, mimicking the MLL recombinome. We anticipate our findings will illuminate this critical phase in cancer initiation and provide a framework to investigate the action of endogenous RNA molecules underlying various genetic aberrations through a process of Endogenous RNA-Directed DNA Damage (ER3D).
Single replicates of each cell line underwent ATAC-seq
 
Overall design John Toubia
 
Contributor(s) Marri S, Conn SJ
Citation(s) 37295428
Submission date Oct 30, 2022
Last update date Jul 31, 2023
Contact name Simon Conn
E-mail(s) simon.conn@flinders.edu.au
Organization name Flinders University
Department College of Medicine and Public Health
Lab Circular RNAs in Cancer Laboratory
Street address Sturt Road, Bedford Park
City Adelaide
State/province South Australia
ZIP/Postal code 5042
Country Australia
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (3)
GSM6697165 HL-60, pMIG (EV)
GSM6697166 HL-60, circMLLe9-10
GSM6697167 HL-60, circMLLT1e2
This SubSeries is part of SuperSeries:
GSE125986 Circular RNAs drive oncogenic chromosomal translocations through R-loop-mediated genome instability
Relations
BioProject PRJNA895903

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Supplementary file Size Download File type/resource
GSE216874_genrich_peaks.xlsx 16.3 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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