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Series GSE129528 Query DataSets for GSE129528
Status Public on Apr 26, 2019
Title Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity [HTGTS]
Organism Mus musculus
Experiment type Other
Summary Topoisomerase II (TOP2) relieves torsional stress during transcription, DNA replication and chromosome segregation, by forming transient cleavage complex intermediates (TOP2ccs) that contain TOP2-linked DNA breaks. While TOP2ccs are normally reversible they can be ‘trapped’ by chemotherapeutic drugs such as etoposide, and subsequently converted into irreversible TOP2-linked DSBs that threaten genome stability. Here, using genomics approaches, we have quantified the etoposide-induced trapping of TOP2ccs, their conversion into irreversible TOP2-linked DSBs, and their processing during DNA repair genome-wide, as a function of time. We find that while TOP2 trapping is independent of transcription it requires pre-existing binding of cohesin to DNA. In contrast, the conversion of trapped TOP2ccs to irreversible DSBs during DNA repair is accelerated two-fold at transcribed loci, relative to non-transcribed loci. This conversion is dependent on proteasomal degradation and TDP2 phosphodiesterase activity. Quantitative modeling shows that only two critical features of pre-existing chromatin structure- namely, cohesin binding and transcriptional activity- can be used to accurately predict the kinetics of TOP2-induced DSBs. Thus, our study permits a mechanistic understanding of TOP2 induced genome instability.
Overall design High-throughput genome wide translocation sequencing (HTGTS) profiles performed in Abelson-transformed pre-B cell
Contributor(s) Andres C, Yaakov M, Shar-yin N. H, Gordana W, Weng T, Guido Z, Elsa C, Nancy W, Amanda D, Jan-Michael P, Keith W. C, Yves P, André N
Citation(s) 31202577
Submission date Apr 09, 2019
Last update date Jan 29, 2020
Contact name Yaakov Maman
Organization name Bar-Ilan University
Department Azrieli Faculty of Medicine
Lab Genome Instability & Cancer
Street address Henrietta Szold 8
City Safed
ZIP/Postal code 1311502
Country Israel
Platforms (1)
GPL16417 Illumina MiSeq (Mus musculus)
Samples (10)
This SubSeries is part of SuperSeries:
GSE129529 Topoisomerase II-induced Chromosome Breakage and Translocation Is Determined by Chromosome Architecture and Transcriptional Activity
BioProject PRJNA531667
SRA SRP191554

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Supplementary file Size Download File type/resource
GSE129528_RAW.tar 4.8 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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