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Series GSE161817 Query DataSets for GSE161817
Status Public on Sep 15, 2022
Title DNA replication timing directly regulates the frequency of oncogenic chromosomal translocations [HiC]
Organism Mus musculus
Experiment type Other
Summary Many cancers originate from misregulation of gene expression caused by chromosomal translocations which result from ligation of DNA double-strand breaks (DSBs). Indeed, translocations may be causal in ~20% of human cancer morbidity 1. Although the sources of DSBs are numerous2-5, we have virtually no knowledge of the steps linking DSB formation to DSB ligation. Here, we show that early replication timing of translocation partner loci, mediated by the activity of replication origins, is a critical regulator of lymphomagenic Myc translocations generated by activation-induced deaminase (AID) during antibody maturation in B-cells. Reduced levels of the replicative helicase, the minichromosome maintenance (MCM) complex6, impairs translocation genesis, decreases firing of replication origins at AID target genes and globally abrogates the replication timing program without altering cell proliferation, gene expression or genome architecture. Strikingly, deleting a single origin of replication at Myc induces a switch from early-to-late replication at Myc with concomitantly impaired translocation frequency. This phenotype is reversed by restoring early replication at Myc thereby demonstrating a direct, causal role of replication origin activity and replication timing in translocation genesis. Finally, this replication timing-mediated step acts downstream of DSBs and is independent of DSB frequency, constituting a novel regulatory step in translocation biogenesis.
Overall design HiC in LacZ and Mcm infected CH12 cells and C13 clone
Contributor(s) Peycheva M, Neumann T, Malzl D, Nazarova M, Schoeberl UE, Pavri R
Citation(s) 36108018
Submission date Nov 19, 2020
Last update date Dec 15, 2022
Contact name Tobias Neumann
Organization name IMP
Street address Campus-Vienna-Biocenter 1
City Vienna
ZIP/Postal code 1030
Country Austria
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (11)
GSM4915147 CH12_HiC_shLacZ_1
GSM4915148 CH12_HiC_shLacZ_2
GSM4915149 CH12_HiC_shLacZ_3
This SubSeries is part of SuperSeries:
GSE161822 DNA replication timing directly regulates the frequency of oncogenic chromosomal translocations
BioProject PRJNA679569
SRA SRP293266

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Supplementary file Size Download File type/resource
GSE161817_CH12_HiC_C13_KI.mcool 1.7 Gb (ftp)(http) MCOOL 1.9 Mb (ftp)(http) BW
GSE161817_CH12_HiC_C13_KI_5kb_domains.bed.gz 24.8 Kb (ftp)(http) BED
GSE161817_CH12_HiC_C13_KI_hiccups.bed.gz 99.4 Kb (ftp)(http) BED
GSE161817_CH12_HiC_C13_deltaori.mcool 2.0 Gb (ftp)(http) MCOOL 1.9 Mb (ftp)(http) BW
GSE161817_CH12_HiC_C13_deltaori_5kb_domains.bed.gz 25.3 Kb (ftp)(http) BED
GSE161817_CH12_HiC_C13_deltaori_hiccups.bed.gz 83.2 Kb (ftp)(http) BED
GSE161817_CH12_HiC_WT.mcool 3.1 Gb (ftp)(http) MCOOL 1.9 Mb (ftp)(http) BW
GSE161817_CH12_HiC_WT_5kb_domains.bed.gz 23.3 Kb (ftp)(http) BED
GSE161817_CH12_HiC_WT_hiccups.bed.gz 95.0 Kb (ftp)(http) BED
GSE161817_CH12_HiC_shLacZ.mcool 1.5 Gb (ftp)(http) MCOOL 1.9 Mb (ftp)(http) BW
GSE161817_CH12_HiC_shLacZ_5kb_domains.bed.gz 27.0 Kb (ftp)(http) BED
GSE161817_CH12_HiC_shLacZ_hiccups.bed.gz 107.4 Kb (ftp)(http) BED
GSE161817_CH12_HiC_shMcm.mcool 1.7 Gb (ftp)(http) MCOOL 1.9 Mb (ftp)(http) BW
GSE161817_CH12_HiC_shMcm_5kb_domains.bed.gz 28.6 Kb (ftp)(http) BED
GSE161817_CH12_HiC_shMcm_hiccups.bed.gz 80.7 Kb (ftp)(http) BED
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