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PLoS One. 2011;6(11):e26054. doi: 10.1371/journal.pone.0026054. Epub 2011 Nov 8.

Next-generation sequencing of apoptotic DNA breakpoints reveals association with actively transcribed genes and gene translocations.

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  • 1A*STAR-Duke-NUS Neuroscience Partnership, Duke-NUS Graduate Medical School Singapore, Singapore, Singapore.


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.

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