Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations.
| dc.contributor.author | Fullwood, Melissa J | |
| dc.contributor.author | Lee, Joanne | |
| dc.contributor.author | Lin, Lifang | |
| dc.contributor.author | Li, Guoliang | |
| dc.contributor.author | Huss, Mikael | |
| dc.contributor.author | Ng, Patrick | |
| dc.contributor.author | Sung, Wing-Kin | |
| dc.contributor.author | Shenolikar, Shirish | |
| dc.coverage.spatial | United States | |
| dc.date.accessioned | 2017-06-01T20:25:34Z | |
| dc.date.available | 2017-06-01T20:25:34Z | |
| dc.date.issued | 2011 | |
| dc.description.abstract | DNA fragmentation is a well-recognized hallmark of apoptosis. However, the precise DNA sequences cleaved during apoptosis triggered by distinct mechanisms remain unclear. We used next-generation sequencing of DNA fragments generated in Actinomycin D-treated human HL-60 leukemic cells to generate a high-throughput, global map of apoptotic DNA breakpoints. These data highlighted that DNA breaks are non-random and show a significant association with active genes and open chromatin regions. We noted that transcription factor binding sites were also enriched within a fraction of the apoptotic breakpoints. Interestingly, extensive apoptotic cleavage was noted within genes that are frequently translocated in human cancers. We speculate that the non-random fragmentation of DNA during apoptosis may contribute to gene translocations and the development of human cancers. | |
| dc.identifier | ||
| dc.identifier | PONE-D-11-13201 | |
| dc.identifier.eissn | 1932-6203 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Public Library of Science (PLoS) | |
| dc.relation.ispartof | PLoS One | |
| dc.relation.isversionof | 10.1371/journal.pone.0026054 | |
| dc.subject | Apoptosis | |
| dc.subject | Base Sequence | |
| dc.subject | Binding Sites | |
| dc.subject | Cell Line, Tumor | |
| dc.subject | DNA Fragmentation | |
| dc.subject | Dactinomycin | |
| dc.subject | High-Throughput Nucleotide Sequencing | |
| dc.subject | Humans | |
| dc.subject | Transcription Factors | |
| dc.subject | Transcription, Genetic | |
| dc.subject | Translocation, Genetic | |
| dc.title | Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations. | |
| dc.type | Journal article | |
| duke.contributor.orcid | Shenolikar, Shirish|0000-0003-0540-6328 | |
| pubs.author-url | ||
| pubs.begin-page | e26054 | |
| pubs.issue | 11 | |
| pubs.organisational-group | Basic Science Departments | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | Pharmacology & Cancer Biology | |
| pubs.organisational-group | Psychiatry & Behavioral Sciences | |
| pubs.organisational-group | Psychiatry & Behavioral Sciences, Translational Neuroscience | |
| pubs.organisational-group | School of Medicine | |
| pubs.publication-status | Published | |
| pubs.volume | 6 |
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