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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 Huss, M
dc.contributor.author Lee, J
dc.contributor.author Li, G
dc.contributor.author Lin, L
dc.contributor.author Ng, P
dc.contributor.author Shenolikar, Shirish
dc.contributor.author Sung, W-K
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.identifier https://www.ncbi.nlm.nih.gov/pubmed/22087219
dc.identifier PONE-D-11-13201
dc.identifier.uri http://hdl.handle.net/10161/14725
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.language eng
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
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/22087219
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
dc.identifier.eissn 1932-6203


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