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| Status |
Public on Jun 28, 2017 |
| Title |
Genome Organization Drives Chromosome Fragility [nsRNA-seq] |
| Organism |
Mus musculus |
| Experiment type |
Other
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| Summary |
In this study, we show that evolutionarily conserved chromosome loop anchors bound by CTCF and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy concomitantly rewire DNA cleavage sites to novel contact domain boundaries. While transcription and replication coupled genomic rearrangements have been well documented, we demonstrate that DSBs at loop anchors are transcription-, replication-, and cell type- independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in acute leukemias and prostate cancers. Thus, loop anchors serve as preferred and promiscuous fragile sites that generate DSBs and chromosomal rearrangements.
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| Overall design |
nascent RNA-seq profile in activated and resting B cells and T cells, with and without transcription inhibition drugs
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| Contributor(s) |
Canela A, Maman Y, Jung S, Wong N, Day A, Callen E, Jung S, Kieffer-Kwon K, Pekowska A, Zhang H, Mckinnon PJ, Aplan PD, Pommier Y, Lieberman Aiden E, Casellas R, Nussenzweig A |
| Citation(s) |
28735753 |
| Submission date |
May 23, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Yaakov Maman |
| Organization name |
Bar-Ilan University
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| Department |
Azrieli Faculty of Medicine
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| Lab |
Genome Instability & Cancer
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| Street address |
Henrietta Szold 8
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| City |
Safed |
| ZIP/Postal code |
1311502 |
| Country |
Israel |
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| Platforms (1) |
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| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE99197 |
Genome Organization Drives Chromosome Fragility |
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| Relations |
| BioProject |
PRJNA387543 |
| SRA |
SRP107841 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE99196_RAW.tar |
1.1 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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