|
| 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.
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| Overall design |
We introduced HTGTS bait DSBs at all mouse autosomes and X chromoosme to map RDCs via proximity in C-NHEJ deficient NSPCs.
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| Contributor(s) |
Wei P, Lee C, Du Z, Schwer B, Zhang Y, Kao J, Zurita J, Alt FW |
| Citation(s) |
29432181, 38678011 |
| |
| Submission date |
Nov 13, 2017 |
| Last update date |
May 24, 2024 |
| 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-Württemberg |
| ZIP/Postal code |
69120 |
| Country |
Germany |
| |
|
| Platforms (1) |
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| Samples (118)
|
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| Relations |
| BioProject |
PRJNA418136 |
| SRA |
SRP124851 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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