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Series GSE106822 Query DataSets for GSE106822
Status Public on Jan 19, 2018
Title Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay
Organism Mus musculus
Experiment type Other
Summary We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations. Cellular heterogeneity in 3D genome organization allowed unequivocal identification of RDCs on 14 different chromosomes using HTGTS baits on three mouse chromosomes. Additional candidate RDCs were also implicated, however, suggesting that some RDCs were missed. To more completely identify RDCs, we exploited our finding that joining of two DSBs occurs more frequently if they lie on the same cis chromosome. Thus, we used CRISPR/Cas9 to introduce specific DSBs into each mouse chromosome in NSPCs that were used as bait for HTGTS libraries. This analysis confirmed all 27 previously identified RDCs and identified many new ones. NSPC RDCs fall into three groups based on length, organization, transcription level, and replication timing of genes within them. While mostly less robust, the largest group of newly defined RDCs share many intriguing characteristics with the original 27. Our findings also revealed RDCs in NSPCs in the absence of induced replication stress, and support the idea that the latter treatment augments an already active endogenous process.
 
Overall design We introduced HTGTS bait DSBs at all mouse autosomes and X chromoosme to map RDCs via proximity in C-NHEJ deficient NSPCs.
 
Contributor(s) Wei P, Lee C, Du Z, Schwer B, Zhang Y, Kao J, Zurita J, Alt FW
Citation(s) 29432181
Submission date Nov 13, 2017
Last update date May 15, 2019
Contact name Pei-Chi Wei
E-mail(s) p.wei@dkfz-heidelberg.de
Phone +496221423251
Organization name German Cancer Research Center
Department Structural and functional genomics
Lab Brain mosaicism and Tumorigenesis
Street address Im Neuenheim Feld 280
City Heidelberg
State/province Baden-W├╝rttemberg
ZIP/Postal code 69120
Country Germany
 
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (118)
GSM2854824 Chr1_APH_ExpA
GSM2854825 Chr1_APH_ExpB
GSM2854826 Chr1_APH_ExpC
Relations
BioProject PRJNA418136
SRA SRP124851

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE106822_Chr10_APH.tlx.txt.gz 2.8 Mb (ftp)(http) TXT
GSE106822_Chr10_DMSO.tlx.txt.gz 2.5 Mb (ftp)(http) TXT
GSE106822_Chr11_APH.tlx.txt.gz 1.3 Mb (ftp)(http) TXT
GSE106822_Chr11_DMSO.tlx.txt.gz 1.3 Mb (ftp)(http) TXT
GSE106822_Chr13_APH.tlx.txt.gz 1.7 Mb (ftp)(http) TXT
GSE106822_Chr13_DMSO.tlx.txt.gz 1.4 Mb (ftp)(http) TXT
GSE106822_Chr14_APH.tlx.txt.gz 1.2 Mb (ftp)(http) TXT
GSE106822_Chr14_DMSO.tlx.txt.gz 2.0 Mb (ftp)(http) TXT
GSE106822_Chr17_APH.tlx.txt.gz 1.2 Mb (ftp)(http) TXT
GSE106822_Chr17_DMSO.tlx.txt.gz 1.8 Mb (ftp)(http) TXT
GSE106822_Chr18_APH.tlx.txt.gz 1.9 Mb (ftp)(http) TXT
GSE106822_Chr18_DMSO.tlx.txt.gz 1.8 Mb (ftp)(http) TXT
GSE106822_Chr19_APH.tlx.txt.gz 2.2 Mb (ftp)(http) TXT
GSE106822_Chr19_DMSO.tlx.txt.gz 1.9 Mb (ftp)(http) TXT
GSE106822_Chr1_APH.tlx.txt.gz 2.3 Mb (ftp)(http) TXT
GSE106822_Chr1_DMSO.tlx.txt.gz 2.4 Mb (ftp)(http) TXT
GSE106822_Chr2_APH.tlx.txt.gz 3.3 Mb (ftp)(http) TXT
GSE106822_Chr2_DMSO.tlx.txt.gz 3.1 Mb (ftp)(http) TXT
GSE106822_Chr3_APH.tlx.txt.gz 1.1 Mb (ftp)(http) TXT
GSE106822_Chr3_DMSO.tlx.txt.gz 1.3 Mb (ftp)(http) TXT
GSE106822_Chr4_APH.tlx.txt.gz 2.5 Mb (ftp)(http) TXT
GSE106822_Chr4_DMSO.tlx.txt.gz 2.0 Mb (ftp)(http) TXT
GSE106822_Chr5_APH.tlx.txt.gz 1.7 Mb (ftp)(http) TXT
GSE106822_Chr5_DMSO.tlx.txt.gz 1.9 Mb (ftp)(http) TXT
GSE106822_Chr6_APH.tlx.txt.gz 2.5 Mb (ftp)(http) TXT
GSE106822_Chr6_DMSO.tlx.txt.gz 1.8 Mb (ftp)(http) TXT
GSE106822_Chr7_APH.tlx.txt.gz 3.2 Mb (ftp)(http) TXT
GSE106822_Chr7_DMSO.tlx.txt.gz 3.1 Mb (ftp)(http) TXT
GSE106822_Chr8_APH.tlx.txt.gz 2.5 Mb (ftp)(http) TXT
GSE106822_Chr8_DMSO.tlx.txt.gz 1.3 Mb (ftp)(http) TXT
GSE106822_Chr9_APH.tlx.txt.gz 2.3 Mb (ftp)(http) TXT
GSE106822_Chr9_DMSO.tlx.txt.gz 1.5 Mb (ftp)(http) TXT
GSE106822_ChrX_Female_APH.tlx.txt.gz 1.0 Mb (ftp)(http) TXT
GSE106822_ChrX_Female_DMSO.tlx.txt.gz 1.5 Mb (ftp)(http) TXT
GSE106822_ChrX_Male_APH.tlx.txt.gz 1.9 Mb (ftp)(http) TXT
GSE106822_ChrX_Male_DMSO.tlx.txt.gz 2.1 Mb (ftp)(http) TXT
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Processed data are available on Series record

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