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| Status |
Public on Jan 31, 2015 |
| Title |
Doxorubicin induces double-strand breaks at CpG island promoters |
| Organisms |
Saccharomyces cerevisiae; Mus musculus |
| Experiment type |
Other
|
| Summary |
Doxorubicin is a widely used chemotherapeutic drug that intercalates between DNA base-pairs and posions Topoisomerase II, although the mechanistic basis for cell killing remains speculative. Here we show that both anthracyclines and Topoisomerase II poison cause enhanced DNA double-strand breaks around CpG island promoters of active genes genome-wide. We propose that torsion-based enhancement of nucleosome turnover exposes promoter DNA, ultimately causing DNA breaks around promoters that contributes to cell killing.
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| Overall design |
We have analyzed mouse squamous cell carcinoma cells treated with doxorubicin, aclarubicin and etoposide. The direct in situ Breaks Labeling, Enrichment on Streptavidin (BLESS, PMID 23503052) method was used for mapping DNA double-strand breaks genome-wide.
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| |
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| Contributor(s) |
Yang F, Kemp CJ, Henikoff S |
| Citation(s) |
25705119 |
| |
| Submission date |
Nov 03, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Jorja Henikoff |
| E-mail(s) |
jorja@fhcrc.org
|
| Phone |
206-667-4850
|
| Organization name |
Fred Hutchinson Cancer Research Center
|
| Department |
Basic Sciences
|
| Lab |
Henikoff
|
| Street address |
1100 Fairview AV N, A1-162
|
| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109-1024 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19379 |
Illumina HiSeq 2500 (Mus musculus; Saccharomyces cerevisiae) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA266225 |
| SRA |
SRP049468 |
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